Table of content
- Endocrinology
- β²Β Hormones Overview
- π«Β Pituitary Gland Disorders
- π¦Β Thyroid Gland
- π Β Parathyroid Gland
- πΒ Adrenal glands
- πΒ Reproductive System
- βοΈΒ Female Reproductive System Disorders
- βοΈΒ Male Reproductive System Disorders
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Endocrinology
β²Β Hormones Overview
- proteins, peptides, monoamines and lipophilic hormones tend to exert their effect primarily through protein receptors at the cell membrane
- steroids, thyroid hormone and vit D tend to operate binding to receptors found in the cytoplasmic or nuclear compartments.
- Long feedback
- Short feedback
- Ultrashort feedback
midcycle E β LH π·
Primary / periph.β Target Gland
Secondaryβ Hypophysis
Tertiaryβ Hypothalamus
Receptorβ Target receptors
βsec + tert = central
- periph. gland defect: low endhormone, high regulatory H
- central defect: both low
- End-Receptor insensitivity [Hormones-resistance-syndrome]: clinical suggestion of H-deficiency, but both are normal/high
π«Β Pituitary Gland Disorders
Neurohypophysis (post. part)
ADH + Oxytocin
NEUROHORMONES (Post Pituitary H) - Vasopressin (ADH) - Oxytocin They are synthesized in magnocellular neurons in the SON and PVN. The neurosecretory granules with ADH and OC travel down the long axons through the stalk to the Post HPF where the granules are stored and then released into the general circulation.
HYPOPHYSIOTROPIC H. / LIBERINE (releasing hormones) / and release inhibiting factors (STATINE) They are synthesized in Parvocellular neurons in PVN (CRH, TRH) and Arcuate N (GHRH, LHRH, dopamine, SS).
Most of the anterior pituitary hormones are under β predominantly positive control by hypothalamic releasing hormones
β exception is prolactin (under tonic inhibition by dopamine)
regulatory hormones = Hypophysiotropic hormones
- within sella turcica of sphenoid
- sup: optic chiasm
- Inf. Sphenoidal air sinuses
- lat: cavernous sinus
girl: 8-13
boys: 9-14
β secondary sex characteristics and internal development, growth
hypothalamic pulse generator in peripubertal period β incr. GnRH β LH+FSH β sex hormones
TANNER π·
- no glandular tissue + no hair
- buds form + small hair
- Elevates + coarse&curly hair
- secondary mound (size+elevation) + adult like hair (thighs spared)
- Adult size + things not spared anymore
before 9 in bois, before (7-)8 in girls
= frΓΌhe kiste π§°
- central (complete true)- premature HPT-HPF axis acitvation (GnRH dependent)
- incomplete - HPT-HPF not acitivated (GnRH independent )
- isosexual
- male:
- female: excessive E (ovarian cyst)
- contrasexual - male: excess E;; female: excess androgen (21-hydroxyl-def)
βexcess hCG or LH by tumor
β excess androgen (21-hydrox.-defic)
central
- idiopathic (most common)
- familial tendency
- CNS disorder (tumor, infection)
- early secondary characteristics (early stage 2 tanner)
- fast growth early but end up as short adults = paradoxical growth
- psychic manifestation
- others β according etiology (i.e. see CNS etiology)
girls
(boys more often delayed puberty)
- Hormones levels (E, T, FSH, LH)
- Goldstandard: GnRH stimulation test (if incr. LH β central cause)
- Radiograph bone age β left wrist or hand
- US ovary + uterus β inc. size, follicles, testicular V + prostate
- MRI / CT mandatory in boys + girls <6y β rule out tumor
GnRH agonist (continous, not episodically β that's why it decr. LH+FSH)
β Triptorelin
GnRH agonists: chronic administration of GnRH has been shown to downregulate GnRH receptors and reduce HPF gland response to GnRH β causing decreased secretion of FSH, LH, and sex steroids
- >13 girl or >14 boys β no signs of of puberty
- Hypogonadotropic hypogonadism
- Kallmann syd
- Multiple pituitary hormonal deficiency
- tumor, trauma, irradiation (HT, PG)
- Hypergonadotropic hypogonadism
- Klinefelter Syndrome
- Turner
Just behind in puberty β shorter (delay for 2SD), normal growth velocity,
β but normal response of LH to GnRH
β observation + psychological support
Somatotrophs (secrete GH β IGF-1)
Gonadrotrophs (secr. LH+FSH)
Thyrotrophs (secr. TSH)
corticotrophs (secr. ACTH)
lactotrophs (secrete PRL)
GH β IGF-1 β growth + metabolism
PRLβmilk production, inhibition of gonadotropin secretion
ACTH β steroids / sex hormones (adrenal)
TSH β Thyroid
LH β androgens β βοΈΒ ovulation, luteinization, maintenance & stimulation of corpus luteum; βοΈΒ sex hormone production in Leydig
FSH β βοΈfollicular development ; βοΈΒ spermatogenesis(sertoli cells)
complex of symptoms and signs caused by an expanding pituitary mass in the sella turcica or the suprasellar space (space between HPT-HPF) π·
ADENOMA (95%)
- micro β <1cm no enlargment/extension
- macro >1cm β sellar enlargment
- nonfunctional
- functional (i.e. prolactinoma)
β DD: Craniopharyngioma, Metastasis, Sarcoidosis, Abcess, Cysts
- Headache (progressive ant+superior + no relief by pain killer)
- hypothalamic synd (conciousness, behavior, thirst, appetite, temperature impairment)
- hypopituitarism + central DI + hyperprolactinemia (loss of dopa inhibition)
- lat extension β cavernous s., CN3,4,6 V1+2 + ICA
- inferior ext. β erosion bony sellar floor+into sphenoid sinus β menigitis
- very large β supra+parasellar ext β inc. ICP β headche, vomit, seizures, papilledema, etc. β π
- bitemporal hemianopia
- (starting superiorly bitemporal)
β confrontational testing (perimetry)
- tumor extension β optic tract β homonymous contralateral hemianopia π·
- CN palsy (3,4,6)
- decr. VA
- optic atrophy + papilledema
Pituitary hypersecretion vs. insufficiency (destruction of healthy tissue)
- hypersecretion β prolactinoma 60% + but also others (GH, TSH, LH/FSH, ACTH)
- nonfunctional β 30%
- ant gland destruction lead to variable signs + symptoms:
Hypersecretion leads to:
Hormone | Clinic |
GH | Children: Short stature. Adults: Reduced exercise, β body fat, β lean body mass, impaired psychological health. |
LH/FSH | Women: Irregular menses, loss of body hair, osteoporosis. Men: ED, testicular atrophy, loss of sexual hair. |
TSH | Similar to primary hypothyroidism but no goiter. |
ACTH | Similar to Addison's disease but without certain symptoms. |
Prolactin | Lactation failure. |
ADH | Excessive urination and thirst. |
MRI π· β gadolinum
micro β no uptake of Gd, <1cm
macro β high uptake, β₯1cm
(CT β calcification, bonedestruction, bleeding)
1. SURGERY 2. RADIOTHERAPY 3. DRUGS: to suppress hypersecretion by the adenoma or its growth.
- Transsphenoidal surgery π· πΊΒ β T of choice (only partial resection of macroadenoma)
- transfrontal / transparietal craniotomy π· πΊ β for the invasive + extending masses
- residual mass or persistent hypersecretion post. surgery
- surgery contraindicated
β Conventional irradiation or Gamma knife
β SE: visual dmg, hypopituitarism(common), seizures, cognitive disorders, radionecrosis
- DOPA agonist in prolactinomaβ Bromocriptine or Cabergoline
- Replacement in insuff
- Somatostatin β acromegaly, TSH-secreting, cushing
- oxytocin β milk ejection, uterine contr. during labor
- Vasopressin (ADH) β incr. water reabsorption in collecting duct β regulate osmolality, water balance + BP
By origin:
- π§ Β CENTRAL DI
- π₯Β NEPHROGENIC DI
By time-pattern:
- β¬Β Transitory DI
- π°οΈ Permanent DI
- Craniopharyngioma most common tumor, producing central DI π·
- surgery + head trauma
- infections + infiltrative disorders
- autoimmune
- idiopathic
- Craniopharyngiomas (the most common solid tumor to produce DI), pituitary infiltration by metastases
- Surgery in the hypothalamic-pituitary stalk area
- Head trauma
- Infiltrative disorders: sarcoidosis, histiocytosis, lymphomas
- Infections: meningitis, meningoencephalitis
- Autoimmune
- DIDMOAD syndrome = DI + DM + optic atrophy + deafness
- Idiopathic
- Acquired
- renal diseases
- hypokalemia + hypercalcemia
- drugs (lithium)
- Familial/genetic (Vasopressin-R (X-linked) vs. aquaporin-2-R (AR))
Any renal disease that interferes with collecting duct or medullary function, e.g., chronic pyelonephritis, toxic nephritis, postobstructive uropathy.
- In adults, polyuria, nocturia, thirst, polydipsia.
- In children, polyuria, enuresis, and failure to thrive.
- Rarely, acute dehydration characterized by arterial hypotension β shock, and coma.
- urine output + osmolarity
- blood osmolarity
- Sodium
- (exclude other causes)
- Dehydration test
- ADH radioimmunoassey
- Vasopressin test: Response to ADH = central DI
Cause investigations:
- MRI β tumor?
- US + IVP β renal pathology?
- polydipsia β dehydration test
- CRF, DM, Hyper-Ca, Hypo-K
Desmopressin + Etiological Tx
Vasopressin analogue, acting predominantly on the V2 receptors in the kidney.
- underlying disorder
- adequate fluid input
- high dose desmopressin
- Thazide diuretics + low Sodium-Diet
- chronic excessive GH β IGF-1 secr
- most commen due to GH-secr. pituitary adenoma
GH β IGF-1 synth. by liver
- IGF-1 binds to IGF + insulin receptors β cell growth + proliferation, inhibit apoptosis
- incr. secretion of Somatostatin β inhibit [neg. feedback]
- lipolysis
β bone, cartilage, skeletal muscles, skin, ST, organs incr. in size
β impaired glucose tolerance (due to action on Insulin-R)
Kidney:
- incr. reabsorption Phosphorus + inc. excretion Ca
- incr. Na + Water reabsorption
- Insulin Resistance
- bone, cartilage, skeletal muscles, skin, ST, organs incr. in size
- lipolysis
- incr. Phosp, Na
- calciuria
- HT (Na + Water)
- gigantism - before ephiphyseal fusion - linear growth (often with hypogonadism) β tall stature
- acromegaly after fusion - no linear growth, local: skull + mandible overgrowth
- GH or GH-PRL secretion pituitary adenoma (most often)
- MEN 1 (Wermer)
- MEN 4
- McCune-Albright synd (MAS)
- Carney complex
- Familial isolated pituitary adenomas (FIPA)
- Paraneoplastic (GHRH-like or GH-like substances)
- Carcinoids (tumors of the endocrine cells which produce hormones)
- Pancreatic, lung tumors
- hypothalamic hamarthoma
β associated with:
- effect of GH/IGF1
- PRL (mixed adenoma or stalk compression)
- tumor mass
ACROFACIAL DYSMORPHISM
- enlarged nose, frontal bossing+supraorbital ridges, prognatism (mandible forward+down),
- teeth separation
- macroglossia, large lips
- deepening of voice + sleep apnea (laryngeal +pharynxhypertrophy)
- hand + feet enlargment (skeletal +SThypertrophy) β thickend + bulky
- thickend skin + acne, incr. sweating (gland hyperplasia)
- hirsutism + hypertrichosis in woman (PRL effect)
- visceromegaly (Thyroid[diffuse, nodular goiter]+salivary gland also heart, silver, kidney,colon
- Hypertension, LVH, valvulopathy, arrhtymias
- Colonic polyps (β colonic Ca) + enlarged colon
- Carpal tunnel syndr. (skeletal m. +ST hyp.) β acroparesthesia
- acromegalic arthropathy (osteoarthritis)
- galactorrhea (PRL)
- Diabetes M
- Hypertrigliceria
- Hypercalciuria + Nephrolithiasis
- Mass effects β hypopituitarism, visual field defect
β incr. in ring, hat, shoes size
- GH
- IGF1
- β supression with oral gluc (OGTT)β healty: reduction of GH to <1ng at 60; acro: failure in supression of GH β gold standard (special for diabetic pat.
- PRL
- assessment of pitutary gland: FSH, LH, E, T; TSH, T4; ACTH, cortisol
- Perimetry β VF defect (bitemp. hemianopsia)
- check Visual acuity
- Thyroids + abdominal US β visceromegaly
- colonoscopy
- check Ca + Phosphrous
- ECG
- CV events
- sleep apnea
- colonic cancer
- neurologic: carpal tunnel
- kidney stones
- Somatostatin analogs
- GH-R antagonist (liver tox)
- DOPA agonist (not only against PRL) - Cabergolin
- surgery (trans-sphenoidal / craniotomy)
- replacement therapy (in insuff)
- Radiotherapy (conventional, gamma knife)
- Prolactinoma (most common)
- Physiological causes: stress, pregnancy, lactation, nipple stimulation, crying baby, sexual orgasm, sleep, exercise
- Damage to Hypothalamus or compression stalk(non-functional macroadenoma or trauma)
- primary Hypothyroidism
- Drugs:
- Dopamine antagonists β Antiemetics(metoclopramide) + Antipsychotics (haloperidol)
- Estrogen + contraceptives
- Antidepressents
- Chronic RF
in macroadenomas β mass effect:
- headache + uni/bitemporal Visual field defect (hemianopsia)
- hypopituitarism
- CN palsies
effects due to high PRL, low LH,FSH,E,T
(high PRLβ galctorrhea, low LH, FSH β menstrual abnormalites, infertility, low testo/estrogen; low testo β decr. libido, erectile dysfunction, gynecomastia; low Estrogen β menopausal sym(i.e. vaginal atrophy), osteoporosis)
- PRL + LH/FSH
- Testo in men
β beta-hcg, TSH+T4, crea β excluded β MRI β prolactinoma
β normal PRL level (>25microg/l)
- consider Visual field assessment
NICE TO KNOW:
β PRL >200 β virtually diagnostic for Prolactinoma
βPRL >250 β microprolactinoma or nonfunctioning supressive macroademia
β PRL > 500 β Macroprolactinoma
β PRL level is correlated with size!
1.line: Dopamine Agonists ( β cabergoline, bromocriptine)
2. surgery (if medical therapy failure; pituitary apoplexy; massive macroprolacinoma)
3. Radiotherapyβ if others fails
- hypothalamic disorder
- Pituitary disorders
- invasive β space occupying mass
- infarction β pituitary apoplexy + Sheehans syndrome
- infiltration β lymphoma, sarcoidosis
- infectious β TBC, syphilis, mycotic
- immunologic β Lymphocytic hypophysitis
- injury (head trauma)
- iatrogenic (i.e. transphenoidal surgery)
- isolated deficiency (i.e. Kallmann sdr.- GnRH) or multiple hormone deficiencies
- Idiopathic
Classic course of acquired loss of anterior pituitary function follows the sequence: GH deficiency -βΊ LH, FSH deficiency - TSH deficiency - ACTH deficiency - PRL deficiency.
- depend on hormones
- GH def β dec. growth, fatique, low muscle mass, incr. fat, osteoporosis, dry skin
- LH+FSH β amenorrhea, loss of seco. hair, breast atrophy, decr. libido, erectile dysfunction, testes atrophy
- TSH β fatique, non-pitting edema, cold intolerance, dry skin, constipation, bradycardia, NO GOITER
- ACTH β weakness, depigmentation, hypotension, hypoglycemia, GI-symptoms
- PRL β no symp in male, failure of lactation in female
- Hypothalamic disorders β variable, visual loss, incr. ICP β Diabetes insipidus
pituitary+target hormones, Stimulation test, MRI, Mass-effect-tests
Measure basal levels of pituitary + target hormone
- gonadotrop function LH, FSH, and testosterone or estradiol.
- thyrotrop function TSH and thyroxine.
- corticotrop function cortisol, ACTH.
- lactotrop function PRL.
- somatotrop function IGF-1, GH.
stimulation test:
- TRH test β TSH level?
- GnRH test β LH+FSH level?
- short synacthen test (ACTH stimulation test) β if cortisol after 30min not high enough β abnormal
- insulin hypoglycemia test β how does the cortisol (ACTH) + GH react to that? β should normally incr.
MRI, opthalmoscopy, perimetry
secondary lab findings
hormone replacement! + underlying cause (i.e. transphenoidal surgery if macroadenoma)
- GH replacement
- Levothyrox
- Predni/hydrocortisol
- Testo + Estrogen,
- for fertility restoration:
- betahcg + FSH in male
- GnRH + FSH/LH in female
- Desmopressin
π¦Β Thyroid Gland
Follicular cell produce Tg (thyroglobulin)β into colloid
idiodide into follicular cell via Na/I symporter (trapping)
β oxidation into iodine (via TPO [thyroid peroxidase]) β bound to Thyrosyl residue of Tg β MIT + DIT
β 2 DIT β T4
βDIT+MIT β T3 (via TPO)
β into vesicle β into follicular cell β lysomomal fusion β hydrolysis of Tg β T4, T3, DIT, MIT β T3+4 into circulation
Thiocarbamide drugs
β i.e. methimazole
bound to TBG, TBPA, Albumin
β only small fraction of T3+T4 is free (0,04% + 0,4%)
only T3 is active there
but T4 is cleaved by cells via deiodinase into T3
release calcitonin (reduce blood calcium, opposing the effects of parathyroid hormone)
malignant β medullary thyroid Ca
Aka Parafollicular cells
- incr. BMR
- incr. cell division
- incr. growth of tissues, organs + bones
- brain maturation (myelination)
- CV effect: incr. HR, incr. contractive force, BP
- incr. GI motility
- incr. Bone resportion (mainly)
- Incr. Energy
- gluconeogenesis, glycogenolyisis
- protein: biphasic: anabolic (physiologic); catabolic (stress)
- lipolysis, incr. TG-synth
TSH
!misleading in secondary cause (HT, pituitary)
T3,4, FT3/4 (free)
β free correlate better with metabolic state + thyroid function
- TRH-stimulation test β high TSH+T4 β secondary vs tertiary (x2 = positive)
- Anti-TPO + anti-thyrogloculin β hashimotos + graves
- US β size, structure β benings vs. malignant
- Scintigraphy β radioiodine β gamma camera β show hyper/hypofunction; ectopic thyroid tissue; hot vs. cold nodule; graves vs thyroiditis
- Fine-needle aspiration biopsy (FNAB) β bening vs malignant nodule
- = simple goiter
- enlargment
- no hyper or hypothyroidism (euthyroid)
- no result of inflammation or neoplasia
- endemic or sporadic nontoxic goiter
- diffuse or multi-nodular
- Auto-immune thyroid disease (i.e. Hashimotos)
- Endemic or Sporadic
- Congenital (defect in TPO)
- Subacute thyroiditis
- Neoplasm (adenoma, carcinoma)
- Drug induced (antithyroid drugs, lithium, amiodaran, TKI, checkpoint inhibitors)
multinodular nontoxic β toxic multinodular (hyperthyroidism)
hashimotos thyroiditis
- enlarged (diffuse or multinodular)
- Compression symptoms
- Pemberton sign β facial flushing + dilation of cervical veins after lifting arms over head (obstruction jugular b. outflow)
- Hoarseness (compression/invasion recurr. laryngeal n. β !carcinoma)
β dyspnea, inspir. stridor, dysphagia,etc
- US β size, nodule no+characterisitcs, lymphnodes, FNAB-guidance
- Scinctigraphy
- Hormones
- Anti-TPO + Anti-Tg (Autoimmune)
- MRI + CT (sourr. structures)
- Larygoscopy: vocal corld paralysis
- FNAB β in malignant suspicion
- uptake of radioactive iodine in scinti
- cold β malignant or benign
- hot β probably benign adenoma (check also if low TSH)
(carcinomas are ineffcient in trapping iodide; most benigsn as well )
- observation with US
- drugs
- iodide β diffuse + young
- Levothyroxine in nontoxic multinodular + diffuse (=suppressive therapy)
- if become toxic multinodular β treat hyperthyroidism
- surgery: growth despite supressive therapy; obstructive symptoms
- Radioactive iodine treatment (131l)β reduce size of massive goiter in eldery+non-indicated for surgery+reoccurence
- Iodide in pregnancy + 6-18y (preventive)
- focal thyroiditis
- dominant nodule in multinodular goiter
- benign adenoma (Follicular π· , HΓΌrthle cell)
- cysts
- postsurgical, postradioiodine hyperplasia
- lipoma, hemangioma, teratoma
- papillary Ca (80%) π·
- Follicular Ca (incl. HΓΌrthle cell Ca) [10%]
β both= differentiated thyroid cancer (respond to TSH)
Type of Malignant Thyroid Tumor | Approximate Frequency |
Papillary carcinoma | 80% |
Follicular carcinoma (including Hurthle cell carcinoma) | 10% |
Medullary carcinoma | 5% |
Undifferentiated (anaplastic) carcinoma | 3% |
Miscellaneous (lymphoma, fibrosarcoma, teratoma, and metastatic cancer) | 1% |
- radiation (esp childhood, head+neck)
- family history papillary + medullary Ca(MEN 2)
- hoarseness
- <20y or >60y
- male
- solitary, firm, non-tender
- fixation to adjacent tissue + lymphadenopathy
- Hashimotos (βlymphoma)
- TSH β high/elevated in malginant
- US: hypoechoic, solic, microcalcification, irregular, "taller than white" β malignant; hyperecho, halo, cystic β benign
- FNAB in suspicious lesion
- Radionucleide scan in low TSH β hot β only observation
- Anti-TPO, Anti-Tg
- Serum calcitonin β elevated in medullary carcinoma
- if histology malignant or suspicious β surgery + Levothyrox for TSH suspression
- Radioiodine ablation in intermedate + high-risk patient with differentiated thyroid cancer
- benign β surveillance if no complicantions
rare
bact. inflammation
β staph, strep, G-, fungus, systemic β endocarditis+sepsis; local extension (pharyngeal infect)
signs of inflammation + infection
β acute, painful, tender, swelling, red, warm
β fever, sweating
β adenopathy
inflammatory markers
- inc. ESR
- anemia
- neutrophilia
normal Thyroid function
US β hypoechoic abcess
FNAB β confirms what etiology
AB + drainage (abcess)
- thyroid inflammation due to viral infection β mumps, adenovirus, coxsackievirus
- after previous resp. infection
infections-signs
- asthenia
- fever
- malaise
- athralgia
- pain over thyroid
- tenderness + nodularity + enlargement
- signs of hyperthyroidism (initially) or hypothyroidism (later)
β extend to jaw or ear loves
- incr. ESR / CRP
- Markers for primary Hyperthyroidism and later Hypothyroidism (appropriate TSH response)
- FT4 + T3 β initally high β progressive drop
- TSHβ initally low β TSH rise when FT4 + T3 drop
- Initially decr. radionucleide (+RAIU) uptake β "white thyroid"
- RAIU rises during recovery
- US β hypoecho
- symptomatic β NSAID, aspirin
- severe cases β predni
- if hyperthyroidism β beta-blocker + sedatives
- if hypothyroidism β Levothyrox
most common cause of hypothyroidism + goiter
autoantibodies against thyroid tissue (Anti-TPO + Anti-Tg)
- painless
- irregular
- rubbery
no goiter π€‘
atrophic thyroiditis
- initially asymptomatic (normal thyroid function) or hashitoxicosis (thyrotoxicosis)
- later: hypothyroidism
postpartum thyroiditis = silent thyroiditis but occurs within one year after birth
"silent" or "painless" thyroiditis is a special form of autoimmune thyroiditis which is presenting as presented below and doesnt cause pain (DD-subacute thyroiditis-pain)
- 1-3month β mild hyperthyroidism
- month β hypothyroid phase
- revocery or permanent mild hypothyroidism (subclinical)
β both of them are not chronic! β only transient
- TSH function (normal, incr. or decr β depends on stage)
- Anti-TPO(90%) + Anti-Tg (25%)
- ESR normal β DD subacute thyroiditis
- RAIU low β DD postpartum Graves
- US β hypoecho
- hypothyroidism
- myxedma
- myxedema coma
!maybe part of multiple Autoimmune-disease
β pernicious anemia, adrenal insuff, DM1, Graves, Lupus,
- only positive Auto-Ab β no therapy
- goiter or hypothyroidism (even mild) β Levothyrox
- Hyperthyroid phase β Beta-blockers
- rare
- intense fibrosis of thyroid β extension into muscles + surroundings (esoph + trachea)
- associated with mediastinal + retroperitoneal fibrosis
- probably due to IgG4-related sclerosis diseases (IgG4-RSD)
- stony-hard mass β DD: malignancy
- euthyroid
surgery if preservation of trachea + esophagus is needed
"ALI Tritt Inder"
- Amiodaron β autoimmune
- Lithium
- Interferon alpha + IL2
- TKI β destructive thyroiditis
- Immune checkpoint inhibitors β autoimmune
- Thyrotoxcisosis with hyperthyroidism
- Graves πͺ¦
- Toxic multinodular g
- Toxic adenoma
- Iodine-induce (Jod-Basedow)
- TSH-secreting pituitary adenoma
- Thyrotoxicosis without hyperthyroidism (not true)
- Thyrotoxicosis factitious (too much Thyroxin snack)
- Subacute thyroiditis
- Thyroiditis with transient thyrotox (postpartum, hashitox)
- Ectopic production (struma ovarii)
- autoimmune
- unknown cause
- CTLA-4 gene + environmental trigger β T-Lymphos sensitized agains thyroid gland β stimulate B-Lymp β TSH-R antibodies (TrAb)
- β thyroid growth, vascularity + hormone production
true follicular adenoma
aka plummers D
somatic mutation TSH-R gene β activation of TSH-R without presence of TSH β small lesions which produces thyroidhormes β progressively more β inhibition of TSH β reduced function of contralateral lobe
- >40y
- recent growth of long-standing thyroid nodule
- symptoms of hyperthyroidism
- no opthalmo- + dermopathy! β DD: graves
- nodule on affected side; reduced tissue on contrallateral side
somatic TSH-R mutation (like toxic adenoma)
long-standing euthyroid (non-toxic) multinodular goiter β incr. in autonomous function β toxic m.g.
- multinodular goiter (large, might extend substernally) π·
- hyperthyroidism symptoms
- no signs of autoimmunity
iodine contraining drugs in patients with iodine deficiency goiter
- amiodarone
- Contrast media
- coronarography
- IVP
- CT
- thyrotoxicosis
- diffuse or multinodular goiter
- Low RAIU
- high urinary iodine
Type 1: excess iodine
Type 2: amiodaron-induced thyroiditis β inflammation β release of T3+T4
- rare
- hyperthyroidism + large goiter
- evtl. other hormones elevated as well
- RAIU markedly supressed (more than i.e. adenoma)
- spontaneous remission (weeks-month)
- teratoma
- mild thyrotox (weight loss + tachycardia β NO goiter or eye)
- mild inc. FT4 + T3
- TSH suppressed
- RAIU low over neck
total body scinti β radioiodine rather in pelvis than neck
β surgery
β CV, CNS, GI, neuromuskular, lipid/protein/Carbs metabolism
High BMR β high BodyT β heat intolerance, sweating, fatique, weakness
- irritability
- insomnia
- shortness of attention
- tremor of hands, tongue, slightly closed eyelids
- Hyperkinesia + hyperreflexia)
due to incr. BMR β more demand + need for heat dissipitation
- tachycardia
- palpitations
- loud heart sounds + systolic murmor
- arrthymias (mainly supraventricular)
- low diastolic high systolic pressure (low periph vascular resistance + high c.output)
- congestive heart failure
- high GI motility β loose stool
- incr. appetite + weight loss
- hepatic dysfunction
- muscle weakness + wasting (high prot. turnover)
- female: impaired ovulation + oligo-/ammenorrhea
- male: erectile dysfunction + gynecomastia
skin: warm, moist, pink (vasodil+sweating)
fine hair β hair loss
- Retraction eyelids β rim sclera betw. lid + limbus β typical stare π·
- lid lag β look down β upper eyelid lags behind globe
- globe lag β look up β lags behind upper eyelid
- lid tremor = Rosenbach's sign
!differentiate from graves!
- diffuse goiter + symmetrical
- smooth
- evtl. bruit + thrill
- exophtalmos, extraoccular muscle dysfunction, diplopia, keratitis, optic neuropathy etc. β see werner classification
- normal upper limit proptosis: 20mm
NO SPECS: π·
2-6 = true infiltrative
extrainfo:
1.(lid retraction, stare, lid + globe lag)
2. +chemosis, proptosis <22mm
3. P >22mm
4. inf. rec β upwardgaze limit; medial β lateral gaze limitation; convergence defect
5. exposure keratitis; P>32mm
6. compression by enlarged muscles or ischemia
clinical activity score π·
>3/7 symptoms β active graves opthalmopathy
- TSH-R on orbital fibroblast + orbital muscles
- cytotix lymphocytes + AB against TSH-R
- cytokines β redness, congestion, conjunctival + periorbital edema
β cytokines
β proliferation fibroblastβ Glycosaminogylcans (GAG)
β preadipocytes β retroorbital fat
β swelling retroorbital fat + muscle by GAGs
βmuscle impairment+diplopia + proptosis
β later muscle fibrosis
smoking
- thyroid acropachy / osteopathy= subperiosteal inflammation on phalanges of hands + feet
- lymphocyte cytokines β stimulation fibroblast
- thickend skin over tibia peau d'orange surface (hyperpig + nonpitting)
- associated with high titer of TSH-R-Ab
other AI-Disease
- DM1
- Addison
- vitiligo
- celiac
- myasthenia gravis
- inc. FT4 + decr. TSH β exception: pituitary adenoma
- Thyroid US
- RAIU + Scinti π·
- Anti-TSH-R β graves
- Anti-TPO, Anti-Tg β hashimoto+graves
- hyperglycemia, low cholesterol, ALP, ECG
- US, CT, MRI β extraoccular muscle
β diffuse enlargement, homogenous, hypoecho β Graves
β one nodule β toxic adenoma
β diffuse inhomogenous, multiple nodules β toxic multinodular g.
β RAIU incr. in thyrotox with hyperthyroidism (Graves, toxic adenoma, toxic multinod)
β RAIU decr. in subacute thyroiditis, postpartum, iodine-induced
β enlarged, symmetic, homogenous β graves
β hot + decr. function in contralat. β toxic adenoma
β multiple functi. nodules; irregular patchy β toxic multinodular g.
- thyroid storm β acute exacerbation all symptoms β fever, flushing, sweating, arrhythmias, HF, diarrhea, vomiting, agitation, delirium, coma
- Cardiothyreosis β arrhythmias (afib), HF, mycardial ischemia
- myopathy β prox muscle wasting in untreated cases
- osteoporosis
- DM
- Hepatopathy β jaundice, heptpatomegaly, ALT+AST
- Methimazole β generally prefered because not hepatotoxic, but teratogenic
- PTU (propylthiouracil) β in pregnancy, hepatotoxic but not teratogenic, and in Thyroidstorm because block periph. conversion T4βT3.
- Symptomatic: Beta-Blocker β Propranolol, atenolol
- Sedatives + MultiVits
- agranulocytosis
- rash
- hepatotoxicity (PTU)
- drug-induced hypothyroidism
generally considered as definite treatment β ATD in general not enough, esp in:
- multinodular goiter or adenoma
- Relapsed Graves
- Allergy to ATD
- Contraindication for surgery
- >80% Hypothyroidism β Levothyrox replacement
- exacerbation of opthalmopathy β give together with predi β dont give in severe opthalmopathy
- Risk group X! β dont give in pregnancy
- Dont give in young children β carcinogenesis
- Symptomatic: Dark glasses, artificial tear, elevated head, diuretics, Selenium
- Glucocorticoids β iv. Methylpredni or oral predni
- Retrobulbar radiation
β consider surgical decompression in severe vision threat and after that surgery for strabismus
β eyelid surgery as final surgery
- primary - most common
- secondary (Pituitary)
- tertiary (HT)
- peripheral resistance
β primary further into: with goiter, atrophic, transient
β congenital vs acquired
Congenital | Acquired | |
I. Primary hypothyroidism with goiter | - Inherited defects in hormone biosynthesis (e.g., Pendred syndrome)
- Endemic cretinism | - Hashimotoβs thyroiditis
- Iodine deficiency (endemic goiter)
- Excessive iodide intake (iodide-containing dye, amiodarone)
- Drugs (interferon alfa, lithium) |
II. Primary hypothyroidism (atrophic) | - Thyroid agenesis
- Ectopic thyroid (lingual thyroid) | - Hashimotoβs disease
- Postablative due to 131I (radioactive iodine therapy), surgery |
III. Transient (postthyroiditis) hypothyroidism | - Subacute thyroiditis
- Postpartum, silent thyroiditis |
- Retardation of mental development
- pretardation of growth β short stature
- puffiness
- Endemic cretism β in regions with endemic goiter
- inherited defects
- Agenesis or ectopic thyroid gland
- jaundice + umbilical hernia
- constipation
- shot stature
- limbs disproportionally short
- impaired mental development
- sparse hair + dry skin
should never be seen
β newborn screening worldwide (TSH+T4 24-48h post-birth)
- retarded growth β short stature
- declining school performance
- precocious puberty
- decr. BMR
- bradycardia
- GAGs in skin, heart, striated muscles β myxedema
- dry, brittle + pale skin
- cold sensitivity
- puffy face, hand, feet (nonpitting myxedema edema)
- dry,brittle hair + nail + Herthoge sign
- decr. appetite + weight gain
- constipation
- intellectual function reduced (speach, hearing, memory) + fatigue, somnolence, lethargy + depression
- slow reflexes
- carpal-tunnel syd, numbness, tingling extremities, muscle weakness
- menstrual abnormalities (menorrhagia)+ infertility,
- loss of libido + impotence
- bradycardia + incr. periph resistance (diastolic p), cardiac enlargement + pericardial effusion
- slow + shallow respiration (β respiratory failure in myedema coma)
- decr. GFR
- other endocrine AI disorders β primary adrenal insuff, DM1, vitilogo, pernicious anemia) β autoimmune polyglandular syndrome (Schmidt's)
- decr. FT4 + elevated TSH β nonappropriate elevated TSH in central cause
- Anti-Tg + anti-TPO
- incr CK + dyslipidemia
- hyponatriemia
- Anemia (macrocytosis β impaired folate intestinal absorption or microcytic β menorrhagia)
- incr. PRL (due to incr. TRH)
- US β variable size + hypoechoic in hashimotos
- RAIU + scinti β assessing inherited defect, agenesis + ectopic
- ECG β reduced QRS,P,T + prolonged QT + PR + sinus bradycardia
- Xray β cardiac enlargment; Echoβpericardial effusion
- Myxedema coma β in longstanding untreated hypothyroidism + triggered by acute event (cold,trauma, infect) βweakness, loss of conciousness, hypothermia, hypoglycemia, hyponatriemia, hypoventilation, shock
- Myxedema cardimyopathy β congestive HF
- Myxedema Pericarditis
- Coronary artery disease (due to incr. lipids)
- Myopathy
- newborn/infants β dwarfism, mental retardation
Levothyrox 1xday before breakfest
β for life! (except transient)
primary β TSH β 6weeks after initiation β then yearly check
central β FT4 β check also glucocorticoids!
pregnancy β incr in TBG (thyroid binding globuline)
β 25-50%
π Β Parathyroid Gland
Incr. Ca + decr. Phosphate in blood +
- incr. Ca reabsorption
- decr. reabsorption Phosphate
- stimulation of aktive VitD in kidney
- incr. intestinal absorption (indirect through VitD)
- incr. bone resorption
- inhibit osteoclast
- inhibit reabsorption of phosphate + calcium
ProVit3 β PreVitD3 β liver β 25hydroxycholecalciferol (Calcidiol) β kidney β Calcitriol (active VitD)
low Phosphate + Ca
high PTH
incr. PTH in:
- decr. Ca
- decr. Mg
- decr. VitD
β &vice versa
high PTH + high Ca β #1primary or tertiary
high Ca + low PTH β others
- malignancies β 2nd most common cause of hyperCa
85% assymptomatic dected by screening
- renal
- stones
- nephrocalcinosis
- decr. GFR
- polyuria + polydipsia
- bones
- osteitis fibrosa cystica β bone pain + patological
- CNS β depression, lethargy, psychosis, lethargy
- Neuromuscular β muscle weakness, hypertonia
- CVβ HT + Bradyc + short QT
- GI βconstipation, pancreatitis, peptic ulcers
- eye β keratopathy
blood:
- high Ca
- Low ( or n) Phosphorus
- high PTH
- high active VitD
urine:
- high Ca
- high Phosphorus
ARE THE OTHER ORGANS GUCCI?
β Renal function test
β Renal imaging
β xray
- Bone mineral density (see osteoporosis)
- Subperiosteal resorption βphalanges + skull (salt+pepper)
- Bone cysts or brown tumor β osteolytic
- pathologic fx
parathyroidectomy
β unilateral if single lesion localized by imaging (Technetium sestamibi scan + US)
β otherwise bilateral exploration β removal of all glands that are enlarged
- hypercalcemia symptoms
- Renal dmg - GFR <60, Renal stones
- Bone diseases: Osteitis fibrosa cystica, T-score > -2.5SD (see later), vertebral fx
- Pancreatitis
transitory post-op hypocalcemia
β hungry bone syndrome + functional inhibition of remaining PT-gland
β give Ca + aktive VitD-metabolite
- Calcimimetic agents β activate Ca-sensing R
β i.e. Cinacalcet
- high PTH
- low Ca
- high Phosphate
- low VitD
- chronic RF
- VitD deficiency
- osteitis fibrosa (cystica)
- Osteomalacia
- Calcitriol (VitD)
- Calicum supplements
- Phosphate restriction (or with phosphate binders)
prolonged secondary β β₯1gland become autonomously (adenoma)
- rhadomyolyisis β flood of Phosphate from injurey muscle β bind all the Ca (PTH + VitD can adapt fast enough)
- Ac. Pancreatitis
- Hungry bone syndrome
- Hypoparathyroidism
- Pseudohypoparathyroidism (Resistance to PTH)
- Failure to produce active VitD metabolit (calicitriol) β Deficiency, Hereditary (Rickets type 1)
- Resistance to VitD-metabolite action β Hereditary Rickets type 2 (defection VitD-R)
incr neuromuscular exitability
β tingling
β numbness
β cramps
β Tetany β Carpopedal spasm (severe: laryngeal spasm)
β Cvostek + Trousseau sign positive π€
- hyperirritability + anxiety + shortness of breath
- prolonged QT
- refractory congestive heart failure (due to impaired excitation-contraction-coupling)
- subcapsular cataracts
- dry + brittle hair, skin, nails
- children β dental hypoplacia + mental retardation
- if VitD-def β lethargy, prox myopathy, bone pain
- if Hypoparathyoidism β mental slowing, personality disturbance, parkinson-like-syndrome, papilloedema
- low Ca
- low PTH
- post-op (thyroidectomy)
- auto-immune (isolated Anti-CaSensitiveR or type 1 polyglandular autoimm. sd: with adrenal insuff + mucocutaneous candidias)
- rare: DiGeorge sd
- infiltration (hemochromatosis, wilson)
- postirradiation (radioactive iodine therapy in graves)
- idiopathic
- urolithiasis (due to lost hypocalciuric effect of PTH)
- renal insuff (hypercalciuria + hyperphosphatemia )
Blood:
- low Ca
- high Phosph
- low PTH
Urine:
- High Ca
- low Phosph
- Calcium supplements orally
- Activated VitD metabolites
- Mg
- Recombinant human PTH (amboss) β lecture: "not yet approved"
- Calcium gluconate i.v.
- Diazepam + anxiolytics
- Oral Ca + rapid acting VitD
- breath into bag (when resp. alkalosis due to anxiety)
- type 1A β same biochemical features + Albright hereditary osteodystopy phenotype β short, round face short neck, obesity, brachydactyly, short metatarsal + -carpals; reduced intelligence
- type 1B β isolated resistance to PTH β
- hypocalcemia,
- hyperPhosp,
- secondary hyperparathyroidism β high PTH
same as hypoparathyroidsm
- low Ca
- low Phosph
- low urinary Ca
- high PTH
- low 25 Hydroxy VitD π·
- Calciferol
- Calcium
primary β postmenopausal + age-related
secondary β thyrotox, glucocorticoids + others that will cause the bone to loose Ca
- hip
- wrist (Colles')
- vertebral compression fx
decr. sexhormones+GH, inc. steroids, incr. T4, inc PTH,
- Endocrine:
- Hypogonadism
- Hyperprolactinemia
- Hyperparathyrodism
- Cushings syd
- Hyperthyroidsm
- GH + IGF-1 def deficiency
- GI β malabsorption syd, Crohns, Liver diseases
- Hematologic d β Leukemia, MM
- Drugs β glucos
silent until acute fracture
β vertebral fx β persistence
Periph fx after low trauma
β no generalized skeletal pain!
Estimate Bone mineral density (BMD) with dual -energy X-ray absorptiometry (DXA) π· β gives T-score
T-score = no. of patients standard-deviation of patient BMD below average BMD
- Xray spine β vertebral fx?
- fracture risk algorithm assessment β clinical risk factor + BMD β 10 year prop for hip-fx + or major osteoporotic fx
- Lab β check secondary causes for low Ca
- ESR + CBC
- ALT + AST
- Urea + Crea
- Ca + Phos
- TSH + FT4
- PTH
- Cortisol
- T/E, FSH+LH
- VitD
incr. BMD + decr. fx-risk
- exercise
- Fall prevention + hip protector
- Good diet (enough Ca + VitD)
Antiresorptives:
- Biphosphonate
- Calcitonin
- SERM + Estrogen
- Denosumab
Osteo-anabolics:
- Recombinant human PTH
- Strontium ranelate
πΒ Adrenal glands
- External β adrenalectomy, chronic corticosteroid Tx
- Destructive internal process
- Autoimmune (most common) β Sporadic, Autoimmune polyendocrine, familial
- Metastasis (SMLungCa, Breast Ca)
- Infection
- Waterhouse-Friderichsen syndrome (meningococcal septicaemia)
- Tuberculosis + other infections
- Genetic - Congenital (adrenal hyperplasia β 21-hydrox-def) β see later extra!!
Reminder: primary = adrenal patho; secondary = hypophyseal patho; tertiary = hypothalamic patho
- Hyperpigmentation (sun exposed + pressure, new scars, buccal+gums after skin)
- Fatigue, Weakness, Weightloss
- orthostatic Hypotension (pos- Schellong test)
- GI-disturb: nausea, vomiting, abd. pain
- Arthralgia
- emotional instability, depression, irritability
- loss sec. hair in woman
- others (related to autoimmune e.g. vitiligo)
- Clinic of HypoNa, HyperK, metab. azidosis
- salt craving (due to Na-loss)
- measure serum Cortisol + ACTH β if high ACTH + low Cortisol = primary; if low ACTh = central/secondary
- β cosyntropin (rapid ACTH-stimulation) test if uncertain i.e. in partial primary β if cortisol <500 β Adrenal insuff (normal <550) β !doesn't mean its primary! β can be secondary or iatrogenic too (due to adrenal atrophy) β only tells you that you have hypoadrenalism
- HypoNa, HyperK
- low Gluc
- inc. BUN + Crea β Volume-depletion
- Anemia + Eosinophilia
- high Renin, high ADH
- ECG β low voltage, ST-modific.
β What's the etiology?
- Adrenal Autoantibodies β Anti-21-hydroxylase, Anti-17-hydroxlase π·
- CT
- serological+Mibi test (i.e. tuberculosis)
β enlarged + Calcification β tuberculosis, metastasis
β small + atrophic β chronic autoimmune
- life long Glucocorticoids β Hydrocortisone, Prednisone
- Mineralcorticoid in primary β Fludrocortisone
- DHEA (Dehydroepiandrosteron) - esp. in female
- enough sodium intake!
- etiological Tx β Infektion, Autoimmune, Cancer etc.
everything should return to normal
- symptoms should disappear + hyperpigmentation should improve
- !overtreatment β cushings
- check Cortisol day curves + ACTH
- Fludrocortison β Electrolytes, BP, Plasma-Renin should be normal
- β Dose of steroids during (Stress, surgery, illness)
- minor stress βincr. 3x3
- major stress (surgery) β up to 200-300mg/day
- pat education: βDonβt miss a dose!β
- Hypotension, volume depletion, shock, coma
- hyperpyrexia
- CNS depression sympt
- GI symptoms like chronic
- hypoglycemia
- weakness + muscle cramps
- Addison + stress (infection, surgery, trauma, dehydration)
- Bilateral acute adrenal hemorrhage (Waterhouse-Friedrichsen syd.)
- Congenital adrenal hyperplasia
draw blood β send to lab
Tx: immediate start with Hydrocortison i.v. + Saline + Gluc i.v.
β donβt wait for lab results before starting Tx
- low Cortisol
- HypoNa, HyperKa, metabolic azid.
- Hypoglycemia
- Eosinophilia
- Urea+ Crea
search for etiology!
βi.e. infection?
deficiency of enzyme (21-hydroxlase) π· in cortisol biosynthesis
β lack of cortisol (+ aldosteron) + overproduction androgens
β Loss of neg. feed back (cortisol) β ACTH hypersecretion β adrenal hyperplasia β incr. accumulation progesterone + 17-OHP β into androgen excess (T, Adrostenedione, DHT)
- Classic CAH
- Salt wasting
- severe reduc. 21hydroxylase activit β dec. cortisol + aldosterol, high androg
- ambigous genitalia in female at birth (cliteromegaly+labial fusion) π·
- male only signs of decr. aldosterone
- Simple virilization
- enough 21-hydroxlase activity to produce sufficient aldosteron β only decr. cortisol + high androgen
- female: less severe masculinization
- male: phallus enlarged
- Non-Classical CAH
- milder 21-hydrox defic.
- Gluc + Aldosterone normal
- overproduction 17OHP β androgen
- female (late childhoof/adulthood): hirsutism, acne, menstrual abnormaltities, infertility
- male: asymptomatic
β untreated: acne, rapid height velocity, advanced growth, precocious puberty, final short height
- clinic
- incr. 17-OHP
- low Cortisol, high ACTH, incr. Renin
- + symptoms of adrenal crisis
- 17-OHP β >15 = CAH; if between 5-15 (normal is <5) β ACTH stimulation test β if exaggerated rise in 17OHP positive for non-classical CAH
- Androgen-level β esp. in female
- Genotyping
classic:
- acute β Hydrocortisone, fludrocortisone, NaCl
- corrective surgery of virilization (in female)
non-classic:
- oral contraceptive
- evtl. Predni
iatrogenic/exogenous(glucocorticoid therapy)
- acth- dependent β pituitary adenoma, ectopic (SCLC) or CRH syndrome
- acth -independent β Adrenal adenoma or carcinoma, iatrogenic, bilateral adrenal hyperplasia/neoplasm (bilateral macronodular, McCune Albright syd, Carney complex)
- central obesity β abdominal, moon facies, buffalo hump
- Thin skin + facial plethora (flushed face)
- abdominal striae
- easy bruising + poor wound healing
- incr. infection + Fungal infection
- Hyperpigmentation of skin in ectopic ACTH
- Hypertension
- Diabetes, insulin resistence
- hyperlipidemiaβ VTE
- Osteoporosis β compression fx
- prox muscle weakness (esp. lower extr)
- children β poor growth + central obesity
- female: virilization, hirsutim, acne, amenorrhea mainly due to high androgens
- male: decr. libido, gynecomasty due to cortisol LH supression
- Renal stones (hypercalciemia)
- drug history β exclude iatrogenous cause
- exclude other causes for stress: illnesses, alcohol, psychiatric etc.
confirmation test β innapropriate cortisol secretion present?? β cushings
- 24-h urinary cortisol >normal
- Low dose dexamethasone suppression test β sufficient suppression of cortisol? β if not cortisol >1,8microg/dl
- Midnight salivary or serum cortisol > normal
β Perform one test first β if positive do another different one (2 test needed for cushing confirmation)
WHATS THE CAUSE?
Measure ACTH
β low β ACTH-independent β CT/MRI Abdomen β Adrenal Adenoma, Carcinoma or Hyperplasia
high β ACTH-depending β high-dose dexamethasone
β fall of cortisol >50% of baseline = prob. pituitary adenoma (cushing disease) β Cranial CT/MRI for confirmation β transphenoidal resection
β no supression β ectopic β search for primary tumor β CT chest abdomen, pelvis
- Androgens (DHEA, androstendione) might be incr. (ACTH-dependent)
- Kalium β hypokalemic alkalosis in ectopic or adrenocortical carcinoma (minderalcorticoid effect)
- fasting Gluc, clinical diabetes test, OGTT
- lipid CHolesterol + TG incr.
- Xray β osteoporotic fx
- TSH+T4, GnRH+FSH+LH, GH
depends on the cause
- iatrogenic β remve source
- Cushing β transsphenoidal surgery β, radiotherapy, βdrugs (steroidgenesis-inhib(Ketoconazole) +ACTHsynthesis-inhibitors(Pasireotidum or Cabergolin)) βbilateral adrenalectomy if severe + cant be controlled otherwise
- Adrenal adenoma β unilateral laparoscopic adrenalectomy
- Adrenal carcinoma β usually already metastasis, surgery β reduce mass+hypersecretion; also consider adrenolytic drugs (mitotane)
- Ectopic β resection, evtl. ketoconazole + K-replacement ; if tumor not found β bilateral adrenalectomy
incr. aldosterone due to primary or secondary cause that typically leads to HT + HypoK
- autonomous hypersecretion with supressed Renin
β Aldosteron producing adrenal adenoma (Conn's synd) 35%
β Bilateral idiopathic adrenal hyperplasia (60%)
βAld produc. Adrenal carcinoma
caused by high Renin
- HF
- Cirrhosis
- nephrotic syd
- renal artery stenosis
- reninoma (rare as shit)
- resistence to conventional anti-HT drugs
- HT + Hypokalemia
- HT <40y
- Adrenal incidentaloma
- When second. HT is suspected
HypoK causes:
- polyuria
- tetany
- myopathy
- periodic paralysis
- metablic alkalosis
β heart + kidney dmg:
- LVH
- CV-events (MI, stroke)
diuretics
only 40%
β normal K does not exclude dg
- Case detection:
- check Na + K β low K
- Check morning PAC + PRA β calculate ARR β ARR>20 + PACβ₯15 β highly suggestive for primary
- normal or high Renin β exclude dg.
- high PAC + high PRA with ARR<10 β second. hyperaldos
- Confirmatory Test
- Detect the Lesion + distinguish betw. Adenoma+ bilateral idiopathy hyperplasia
- Adrenal CT β Adenoma hypodense nodule <2cm β if in doubt β Adrenal venous sampling: measure Aldosterone from both adrenal veins β gradient betw. too = unilateral diseaes β no gradient bilateral
- βonly do that if you wanna do surgery
Saline infusion 2l for 4h β if no aldosterone supression? β positive primary
Condition | Aldosterone | Renin |
Primary aldosteronism | β | β |
Secondary aldosteronism | β | β |
Mineralocorticoid excess, other than Ald (e.g., DOC or corticosterone, ectopic ACTH sdr, 11 Ξ²-hydroxilaza deficiency) | β | β |
π§πΎββοΈ: I've formatted the information to match the table structure. Does this look good to you? What would be the next step? π
Adenoma β unilateral laparoscopic adrenalectomy
Bilateral idiopathic hyperplasia β Sprironolactone or Eplernone
4 π· β 4th only in adrenal medulla because PNMT needs high Cortisol levels to work properly
rare π₯΄
Pheo:
- 90%
- chromaffin cells of adrenal medulla
- most tumors secrete E+NE (large only NE)
Para:
- 10%
- extra-adrenal symp + parasymp nervous tissue
- typically in head + neck but can also be at thorax,pelvis, bladder
- Only NE
- HT-crisis
- malignancy extension (15-20% = malignant)
- π₯Β sporadically (most common)
- Genetic: Mutations in tumor suppressor gens (β uncontrolled proliferation β tumors)
- MEN (2A + 2B)
- Neurofibromatosis 1
- Von Hippel-Lindau disease
β or Succinate dehydrogenase (SDHD)mutation (increased accumulation succinate β inc. free radicals β tumor)
βalso check family history
- mutations associated with P or PGL
- family history of MEN2 π·
- young with HT
- severe HT
- resistance to conventional HT-treatment
- HT crisis during anestesia
- Adrenal incedentaloma
- HT (sustain or episodic)
- resistance to conventional HT-therapy
- but also hypotension,shock possible
- palpitation, headach,sweating
- pallor
- paresthesia, visual distubance, seizures, dyspnoe, weigh loss, hyperglycemia
- Complication:
- LFV, dilated Cardiomyopathy
- pulm. edema
- HT encephalopathy
- check plasma free metanephrines
- urinary fractionated metanephrins
β if inc. 2x upper limit normal β highly suggestive
- clonidine supression test βpotentially dangerous!
- Chromagranin A β detection of nonsecretory tumors (paragangliomas)
- others like Plasma-fractioned Catecholamines + urine fractined catecholamines might be incr. too
localization!
β CT abdomen, pelvis (thorax for parag.)
β MRI abdomen, pelvis , skull β dg. for P + PGL and metastatis
β Scinti β Metasitasis + whether adrenal mass = pheochromocytoma
β PET with FDAβ metastasis
All cases should be considered, esp.:
- bilateral tumor
- extraadrenal
- malignancy
- family hist
- young age
SURGERY
small + benign pheoc β laparoscopy
>6cm or invasive pheo β open resection
parag β open resection (lapa if small+noninvasive + easy location)
controll BP β normotensive!!
β pre-operative blockade started 7-14days prior
β alpha-adrenergic blocker
β Ca-channel blockers (instead or together with alpha-blocker)
β beta-blocker (only in combination with alpha!!
πΒ Reproductive System
βοΈΒ Female Reproductive System Disorders
- primary β failure of onset by 16years
- secondary β no menses for >6month/>3cycles with previously existing menses
<9 periods / year
secondary (central, hypogonadotropic hypogonadism) = diseases of hypothalamus/pituitary gland
vs.
primary (peripheral, hypergonadotropic hypogonadism) =ovarian failure
before puberty
vs.
after puberty
- PCOS
- Hypothalamic amenorrhea
- Hyperprolactinemia
- Ovarian insuff.
primary: Gonadal agenesis, dysgenesis (Turner)
secondary: Kallmann syd. (low GnRH), constitutional delay in puberty, neoplasm (pituitary), pituitary insuff
- Primary: Premature ovarian Failure
- Iatrogenic
- Turner Mosaicism
- Infection
- AUtoimmune
- Secondary:
- Hypothalamus
- Functional β Stress, eating disorder, strenous exercise
- Chronic diseases
- Neoplasm
- Pituitary
- Hyperprolactinoma + other pituitary tumors
- Acquired pituitary insuff
- sexual infantilism
- prim. amenorrhea
- absence pubic + axillary hair
- absence of breast develop
- infantile genitalia (ext+int)
- Somatic modific.
- tall + eunuchoid skeleton π·
- Psychological:
- decr. libido
- second. amenorrhea
- infertility
- decr. in second. hair
- atrophy breast
- involution genital tract + urogenital atrophy
- precocious wrinkles
- hot flushes
- osteoporosis + arterosclerosis
- rule out Hypothyroidism + Prolactinemia β TSH, FT4, PRL
- Primary vs. Secondary β FSH, LH, E2
βif secondary β GnRH-test β delayed puberty vs. more serious
β if primary β short stature β Turners β Bar + Karyotype
βif primary β normal height or eunucoid properties β other causes β Autoimmune (Anti-ovary AB), morphological abnormalities ovary + uterus (Sono, Celioscopy +Biopsy)
- Rule out pregnancy
- Check TSH, FT4, Prolactinoma
- Check if there is endogenous Estrogen production
- Insuff. E production
- Normal E, Outflow tract defect
- Signs of hydroandrogenism (Hirsutism, acne) β evaluate PCOS, late CAH, Cushings
β measure E2 levels
β Progesterone withdrawal test β exog. Progesterone 5-10days β 1 week after last pill β bleeding? β positive: Estrogen synth. possible but anovulation
β Negative:
β HT-P-dysfunction
β primary ovarian failure
β check FSH,LH,E2 to differentiate
β give oral E+P β no bleeding β positive:
due to:
βAsherman's snd
βMullerian defects
HRT (Sex Hormone replacement therapy)β Estrogen β EE2 5microg/day or conjugated E β add MPA (progest) at day 12-21 after physical signs + breakthrough bleeding occur and always 6month after start of the treatment
βeasy to switch to oral contraceptives later
HRT β E+Pβ sequential or continous
β 21days: Cyclo-Progynova
β28 days: Femoston
β if adolescent or woman without uterus β only E (without P)
β GnRH or FSH+LH when fertility desired (in central)
12 month of amenorrhea
(FSH is typically β₯40mIU/ml)
mean = 50
Early <40y
- PCOS (95%)
- Adrogen-secr. tumors (ovaries + adrenals)
- Cushings
- Acromegaly (due to PRL+Insulin effects)
- Insulin resistance (insulin effects)
- Idiopathic
- Drugs
inducing factor might be obesity which leads to insulin-resistance
- Insulin Sensitivity & PCOS:
- Context: Decreased peripheral insulin sensitivity is characteristic of PCOS, similar to metabolic syndrome.
- Consequence: Rise in insulin levels known as hyperinsulinemia.
- Effects of Hyperinsulinemia:
- Obesity: Direct correlation.
- Skin Changes: Epidermal hyperplasia and a distinct darkening called acanthosis nigricans.
- Hormonal Disturbances:
- Androgen production escalates in the ovarian theca cells β leading to an imbalance in androgen precursors and estrogen from granulosa cells.
- LH secretion disrupts the LH/FSH balance β Resulting in anovulation and oligoovulation.
- Increased release of androgen precursors β virilization with a subsequent surge in estrogen synthesis within adipose tissue.
- Decrease in SHBG (sex hormone-binding globulin) production in the liver β more free androgens and estrogens.
- Highlight: A dominant cause of hyperandrogenism in women is PCOS.
- hirusitism + high androgens + chronic ameno-/oligomenorrhea OR Polycystic ovarian morpholgy
- + exclusion of other causes for hirsutims
menstrual abn, infertility, hirsutism, acne, androgenic alopecia, insulin R, obesity
- oligo-/amenorrhea
- anovulation
- hirsutims
- seborrhea + acne
- androgenic alopecia
- insulin-R
- obesity
- infertility
in the blood?
- high Testo
- Low SHBG
β rule out others: PRL, TSH+Ft4, 17-OH-Progesterone (late CAH)
weight loss! β high associated obesitiy with hyperinselinemia
- oral contraceptives
- Androgen-R blockers
- laser hair removal
- Metformin
complete/partial absence of 1 X-chromosome β 45,XO (or Mosaicism)
- Somatic abnormalities
- micrognathia (small jaw)
- fish-like mouth
- high-arched palate
- Hypertelorism
- low-set ears
- webbed neck
- low post. hairline
- broad chest + wide spaced nipples
- short 4th metacarpal bone
- cubitus valgus
- Aortic Coarctation
- horseshoe kidney + double pelvis + ureter
- osteoporosis + scoliosis
- Sexual infantilism at puberty
- premature apoptosis of ovarian follicles β fibrous
- immature int+ ext. genitalia
- Short stature
- Due to SHOX-gene located on X
β primary amenorrhea
β sexual infantilism
- Karyotype β 45XO or mosaicism
- Barr test β negative
- FSH+LH high; E low
- Xray β short 4th metacarpal, scoliosis, osteoporosis
- Cardiac evaluation: MRI + Echo
- IVP+Renal sonography
- US of pelvis +MRI β rudimentary fibrous ovaries(=streak gonads), small uterus
- recombinant GH (45-50 microg/kg/day)
β after reached acceptible height
- Estrogen therapy
β 2years after or after breakthrough bleeding:
- Progesterone therapy
βοΈΒ Male Reproductive System Disorders
- primary
- secondary /central
- Androgen insensitivity
- bilateral anorchia (vanishing testes syd)
- Klinefelter sdr
- Noonan snd.
- Iatrogenic: trauma, radiation
- Orchitis
- Cryptoorchidism (undescended testies)
- panhypopituitarism
- isolated FSh+LH deficiency
congenital:
βKalmann snd. or Prader-Willi
acquired:
β Hyperprolactinoma, TUmor, Cushings, Head trauma, Radiotherapy
- 2-3 month of fetal develop β genitalia ambiguity + male pseudo-hermaphroditism
- during 3 trimester β cryptoorchidism + micropenis
β poor 2nd sexual characteristics + eunuchoid skeleton
- small testes + penis
- no rugae development of scrotum
- no second. hair (axill, pubic, facial, chest, abdomen, back)
- No erections
- inadequ. spermatogenesis
- eunuchoid skeleton + tall
- low muscle mass + abdominal+pelvic adipose tissue
- low bone mass
- high voice
- pale skin + precocious wrinkles
- decr. libido
- low libido + energy
- erectile dysf
- atrophy of testes + prostate
- spermatogenesis disturbances
- infertility
- reduced beard growth
- pale + wrinkles
- central fat
- muscle hypothrophy
- gynecomastia
- osteoporosis
- anemia
- hot flushes
- total T (7-10am)
- LH + FSH
- suggestive for secondary(low FSH+LH)
- suggestive for primary (high FSH+LH)
- Others:
- Semen anlysis β normal semen = exclusion of gonadal dysfct.
- Scrotal US β Volume, Doppler
- Testicular biopsy β in normal size testes + azoospermia β spermatogenic failure vs. ductal obstruction
β measure PRL + do pituitary function test, imaging + neuro-optha exam
β GnRH test β esp. usefull for delayed puberty vs. destructive pituitary lesion
β chromosomal anylsis β genetic (klinefelter) vs. acquired
β hCG stimulation test β differentiation cryptoorchidism + anorchia β T incr. in crypto; no response in anorchia
Testo replacement
β Testosterone enanthate i.m.
β Testosterone undecanot
β Androgel
β start only at age of 13!!
-gynecomastia
-erythrocytosis
-sleep apnea
nope
β in secondary hypogonadism consider exogenous hCG+FSH injection for spermatogenesis + virilization
47XXY (or more) or mosaic due to maternal meiotic nondysjunction
- hylainization+fibrosis of seminiferous tubules β absence of spermatogenesis
- Leydig cells also abnormal β low Testo
degree on decr. T production
- Tall β long leg lenght but arm spann is less than total height (not truely eunuchoid)
- Small, firm testes
- penis small (but variying some actually normal)
- gynecomastia
- decr. libido + erectily dysfunction
- decr. second. hair
- osteoporosis
- cognitive impairment + poor impulse control, dissocial behavior
- Karyotyping
- T dec., FSH+LH incr. (FSH>LH)
- Semen analyiss β Azoospermia (aka Platzpatronen)
- bar test β positive
- Androgen replacement
- Mamoplasty
- Sperm extracted directly from testes β ICIS
