Hypothalamic-Pituitary Axis Flashcards
Which type of cells are rarely clinically functional in an adenoma?
Gonadotrophs
From where is IGF-1 secreted? What triggers this?
Liver, along with other somatomedins in response to growth hormone
Rate limiting step of cholesterol biosynthesis
Cholesterol side chain cleavage enzyme (P450scc/CYP11A1/desmolase) cleaves off 6-carbon side chain to yield pregnenolone
First step of cholesterol biosynthesis
Cholesterol side chain cleavage enzyme (P450scc/CYP11A1/desmolase) cleaves off 6-carbon side chain to yield pregnenolone
21-alpha-hydroxylase deficiency- presentation
- Decreased cortisol
- Increased androgens causes virilization of female (shunting)
- Decreased aldosterone leads to salt wasting
Where does vitamin D regulate intestinal calcium absorption?
Duodenum
Graves’ disease- ultrasound findings
Diffuse enlargement with high vascularity
Sheehan’s syndrome- presentation
Postpartum hypopituitarism. Acute presentation may include failure to lactate and hypotension/tachycardia (even after correction for blood loss and hypoglycemia). Presentation may also be chronic/late.
What is familial hypocalciuric hypercalcemia?
A rare disease caused by an inactivating mutation of CaSR. Chief cells do not sense high free calcium, so they keep secreting PTH. Kidneys keep reabsorbing calcium.
What is cushinoid syndrome?
Iatrogenic cause due to oral corticosteroids for immune suppression
Hypothyroidism- symptoms
Weakness, lethargy, somnolence, slow speech, cold intolerance, memory impairment, constipation, weight gain, dyspnea, menorrhagia, hair loss, myxedematous edema
123-iodine scintigraphy- toxic multinodular goiter findings
Non-uniform uptake with hot and cold areas. Uptake in upper normal or mildly elevated range
Conn syndrome- causes
adrenal adenomas, adrenal hyperplasia, aldosterone-producing adrenocortical carcinoma, familial hyperaldosteronism, ectopic aldosterone-producing tumors
What is hypercalcemia of malignancy?
Malignant tumor secretes PTHrP, excess calcitriol production, or osteolytic bone metastases
Acromegaly- diagnosis
Serum IGF-1 level or lack of GH suppression during oral glucose tolerance test; MRI to confirm
What is sacrificed in a radical lateral dissection of the neck?
sternocleidomastoid, CN-XI, internal jugular vein
What do acidophiles in the pituitary gland secrete?
Prolactin and growth hormone
Pheochromocytoma- classic triad
1) Sustained or paroxysmal HTN
2) Headache
3) Generalized sweating
M1CR ligand and function
MSH and ACTH are ligands; simulates melanin production
Adrenal cortical adenoma pathophysiology
Well defined, may be encapsulated, yellow to black color, rarely foci of necrosis. Neoplastic cells resemble normal cells. Clear, lipid-filled cells in sheets/nests. Uninvolved gland shows lipid-depleted, compact cells.
Pheochromocytoma cell type
Tumor of catecholamine-producing chromaffin cells
Enzyme that changes steroid from glucocorticoid path to androgen path
17,20-desmolase
Most common cause of primary hyperparathyroidism
Solitary single adenoma
Anaplastic/undifferentiated thyroid carcinoma- presentation
Very poor prognosis. Highly aggressive tumor in the elderly. Often kills by direct airway invasion.
Diabetes insipidus- presentation
Polyuria, polydipsia, hypernatremia, high plasma and low urine osmolality
11-beta-hydroxylase deficiency
- Decreased cortisol
- Increased mineralocorticoid activity (non-aldosterone mineralocorticoids with loss of negative feedback by aldosterone; elevated DOC [protein S])
- Increased androgens in utero
Blood supply to adrenal glands
Superior (from aorta), middle (from renal), and inferior (from renal) adrenal arteries
Inheritance pattern of congenital adrenal hyperplasias
Autosomal recessive
Neuroblastoma- presentation
- Infant/child
- abdominal mass
- fever
- weight loss
- opsoclonus myoclonus syndrome (OMS)
- Secretion of vasoactive intestinal peptide (VIP)
Factors regulating prolactin secretion
Releasing factors:
Oxytocin (need milk), TRH, others
Inhibiting factors:
Parvocellular dopamine, prolactin negative feedback on lactotrophs and activation of arcuate nucleus for DA secretion
PTH function
1) Increase DCT reabsorption of calcium (TRPV5)
2) Inducer of 1-alpha-hydroxylase to catalyze final step of calcitriol synthesis from calcidiol
3) Stimulates clearance of renal phosphate
4) Stimulates activity of osteoclasts by inducing RANKL expression in osteoblasts
Thyroid surgery complication causing breathy hoarseness
Unilateral recurrent laryngeal nerve injury
Pre-biosynthetic step of steroid hormones that is a rate-limiting factor
Transport of free cholesterol across outer mitochondrial membrane by steroidogenic acute regulatory protein (StAR)
How do the parathyroid glands sense calcium?
Calcium-sensing receptor (CaSR) on chief cells
What do you think when you see 2 or more parathyroid adenomas?
MEN1
MEN2 genetics
Autosomal dominant pattern. Gain-of-function RET mutation (chromosome 10). RET is a receptor tyrosine kinase. Activates MAPkinase cascade. Mutation causes constitutive growth signal in absence of GDNF (ligand).
Prolactinoma treatment
Dopamine agonists are first line.
- Cabergoline
- Bromocriptine
LH/FSH deficiency- presentation in women
Amenorrhea/oligomenorrhea, infertility, breast atrophy, vaginal dryness; note- no change in pubic and axillary hair (only source of androgens is adrenal gland, which is unaffected)
Common cause of gigantism
Growth hormone excess (often a GH/PRL adenoma) prior to epiphyseal plate closure
Where does RANKL bind?
Pre-osteoclasts, causing them to mature
Hashimoto’s thyroiditis- pathology
- Glandular enlargement (diffuse goiter)
- Lymphocytic infiltrate with germinal centers
- Atrophic follicles
What is the pyramidal lobe?
Most caudal remnant of the thyroglossal tract, present in 1/3 of normal subjects
What is pseudohypoparathyroidism?
Receptor mutation causes PTH resistance
Hypophysitis- pathophysiology
Lymphocytic or granulomatous (TB/sarcoid)
What is MEN2A ?(Sipple syndrome)
Medullary-thyroid carcinoma (amyloid-producing) with pheochromocytoma and hyperparathyroidism
Graves’ disease presentation
Nervousness, fatigue, weakness, sweating, heat intolerance, tremor, hyperactivity, palpitations, appetite decrease, weight loss, menstrual disturbance, Graves’ opthalmopathy (variant of lid lag sign of thyrotoxicosis), Graves’-associated dermopathy (pretibial myxedema)
Lipoid congenital adrenal hyperplasia
Rare; accumulation of fatty deposits in the adrenal gland on biopsy due to accumulation of cholesterol. Genetic defects in StAR or cholesterol desmolase.
What metabolite is used to determine vitamin D deficiency?
Calcidiol (25-hydroxycholecalciferol, made in the liver from vitamin D3)
Central compartent of neck- level and boundaries
Level VI; hyoid bone (superiorly), carotid arteries (laterally), innominate artery (inferiorly)
Remnants of the thyroglossal duct that do not degenerate
Thyroglossal duct cysts, ectopic thyroid gland
Cushing syndrome- pathophysiology
Systemic disease due to chronic glucocorticoid excess
Thyroid hormone synthesis
Iodide is taken up from serum by the sodium-iodide transporter (NIS). Thryoglobulin is synthsized and exocytosed into the follicular lumen (colloid). Free iodide is transported into the follicle by pendrin, and it is oxidized to iodine by thyroid peroxidase (TPO). Iodination of thyroglobin tyrosine residues generates monoiodothyronine (MIT) or diiodothyronine (DIT). Conjugation of two of these products generates T3 or T4. If the MIT is the inner tyrosine, then it is inactive reverse T3. Iodinated is endocytosed, fusing with the lysosome to form the lysoendosome. Proteolysis liberates T3, T4, and RT3.
What non-IGF-1 receptor does IGF-1 bind?
Insulin receptor (insulin-like effects)
Where is calcium reabsorption hormonally controlled? What is the name of the channel?
In the distal convoluted tubule via TRPV5 (upregulated by PTH)
Pituitary apoplexy- pathophysiology
Sudden hemorrhage, often secondary to adenoma as it lays down new, leaky vessels
Fludrocortisone use
Low aldosterone activity (high affinity for mineralocorticoid receptor)
Effect of growth hormone on blood glucose
Diabetogenic: decreases glucose uptake by muscle and adipose, increases lipolysis
123-iodine scintigraphy- Toxic adenoma/nodule findings
Single hot nodule, suppression of the rest of the thyroid gland, uptake generally in normal range
What/where are the magnocellular neurons?
They originate in the paraventricular and supraoptic nuclei of the hypothalamus and go through the infundibulum to the neurohypophysis. They synthesize and secrete ADH and oxytocin
Aromatase actions
1) Androstenedione to estrone
2) Testosterone to estradiol
What blocks Levothyroxine absorption?
Calcium, soy, iron (CSI)
Metabolic effects of cortisol
- diabetogenic, mobilizing glucose
- mobilizes amino acids and glycerol backbones for gluconeogenesis
- “planning for stress”
Embryological origin of the neurohypophysis
Diencephalon; evagination termed the infandibulum
Medullary thyroid carcinoma- pathology
Organoid appearance with nests and cords. Immunostain for calcitonin.
Factors that regulate growth hormone release
Stimulatory: GHRH, ghrelin, low glucose, low FFAs, fasting, puberty, hormones, exercise
Inhibitory: somatostatin, GH and IGF-1 (negative feedback), high glucose, high FFAs, obesity, pregnancy
Medications for acromegaly
Octreotide and lanreotide (somatostatin analogs), pegvisomant (mutated GH receptor), cabergoline (only on STEP)
123-iodine scintigraphy- procedure
Give oral dose of iodine, then scan in 24 hours. Measure 24-hour uptake in thyroid.
Pituitary macroadenoma- presentation
1) Hormone excess/deficiency
2) Bitemporal hemianopsia
3) Headache (dura stretching)
4) Hydrocephalus (compression of CSF system)
5) Diplopia (CN-III) or other cranial nerve palsies if there is lateral extension
Pheochromocytoma- lab findings
- Elevated plasma metanephrines
- Elevated 24-hour urinary catecholamines and metanephrines
- Homovanillic acid and vanillylmandelic acid
What medications increase levothyroxine requirements?
Estrogen, antidepressants, anti-seizure meds, reflex meds
Congenital defect associated with hypoparathyroidism
DiGeorge syndrome
Hyperparathyroidism- presentation
Hypercalcemia symptoms, fractures, osteitis fibrosa cystica, GI symptoms, neuropsych, HTN, shortened QT, nephrolithiasis, band kerotopathy
Adrenal cortical carcinoma- hereditary syndromes
Li-Fraumeni, Beckwith-Wiedemann, MEN1
Hypoaldosteronism- diagnosis
History, plasma renin activity, serum aldosterone, serum cortisol
Hashitoxicosis- presentation
Similar to Graves’ at first (may even have antibodies) but then patients become hypothyroid due to changes in the immune reaction
What happens when the Rathke’s pouch fails to regress?
Pharyngeal hyopphysis, Rathke cyst, craniopharyngioma (benign)
Conn syndrome- treatment
Surgery is ideal if unilateral. Medications include mineralocorticoid antagonists (spironolactone, epleronone) and potassium-sparing diuretics (amiloride, triamterene)
Mineralocorticoid zone
Zona glomerulosa
Sources of cholecalciferol (vitamin D3)
1) de novo from cholesterol
2) dietary (fish, eggs, fortified milk)
Hypoaldosteronism- causes
- Hyporeninemic hypoaldosteronism, associated with diabetic nephropathy and chronic nephritis
- Medications, such as NSAIDs and ACE inhibitors
- Addison’s disease
- Inherited disorders (e.g. aldosterone synthase deficiency)
Pathway activated by growth hormone
JAK-STAT; mutations in this pathway can cause GH insensitivity/dwarfism
Inferior parathyroid glands embryological origin
Third pharyngeal pouch
Hypocalcemia treatment
IV calcium, oral calcitriol in acute cases. Oral calcium and cholecalciferol for maintenance.
Lid-lag sign of thyrotoxicosis
Result of hyperadrenergic effects. Sympathetic stimulation of Muellers muscle (superior tarsal plate).
For which type of pituitary adenoma is surgery NOT the primary treatment?
Prolactinoma
Drugs that interfere with thyroid function
Tyrosine kinase inhibitors, lithium, amiodarone, interferon-alpha
Iodine for treatment and particle(s)
Iodine-131 (gamma and high-energy beta)
Common cause of mortality in acromegaly
Cardiovascular disease (HTN, LVH, cardiomyopathy)
Portion of adrenal cortex that appears to be “tubular”
Zona fasciculata
Hyperthyroidism- treatment
Thionamides, (Methimazole, Propothiouracil) block oxidation of iodine by TPO. Propothiouracil also blocks conversion of T4 to T3. Radioiodine (I-131) can be used to ablate the thyroid.
Other name for toxic multinodular goiter
Plummer’s disease
Three forms of calcium
1) free (majority)
2) protein-bound (albumin)
3) complexed to anions (least)
What happens to pregnenelone in the zona glomerulosa?
Converted to progesterone by 3-beta-hydroxysteroid dehydrogenase
Most common RET mutation in MEN2B
Methionine switched for threonine (M918T) at codon 918
Most important regulator of TSH levels
Free T4. Remember, most T4 is bound to thyroid-binding globulin, TBG.
Hashimoto’s thyroiditis- ultrasound
Hypoechoic appearance
Follicular thyroid carinoma- presentation
Good prognosis. More common in women 40-60. Produces thyroglobulin. Hematologic spread more common, especially to bone. Requires histology for diagnosis.
Imaging agent taken up by any cells expressing catecholamine intake
Metaiodobenzylguanidine (MIBG)
Neuroblastoma cell type
Neuroblast cells (primitive sympathetic ganglion)
Embryological origin of the adenohypophysis
Evagination of oral ectoderm (Rathke’s pouch), which regresses
Iodine for imaging and particle(s)
Iodine-123 (gamma)
Which adrenal vein is more difficult to cannulate in adrenal vein sampling?
Right side. Enters IVC directly at an acute angle.
Graves’ disease- pathology
Follicular cells become columnar in shape. Active resorption of thyroglobulin. Infolding of epithelium. May progress to lymphocytic infiltrate and destruction of follicles, resulting in hypothyroidism.
What is the normal function of PTHrP
Secreted by mammary gland in lactation, mobilizing calcium for milk production.
How does iodine cause HYPOthyroidism?
Inadequate synthesis of T4. Compensatory TSH causes hyperplasia, resulting in a diffuse goiter.
Most common hormone-secreting pituitary adenoma
Prolactinoma
Sheehan’s syndrome- pathophysiology
The adenohypophysis is enlarged during pregnancy with no additional blood supply. A superimposed peripartum hemorrhage can cause an infarction due to hypovolemic shock.
Mitotane
Breaks down entire adrenal cortex
Cortisol-cortisone shunt- mechanism
Kidneys (and colon, sweat glands, salivary glands) express 11-beta-hydroxysteroid dehydrogenase 2, which converts cortisol to cortisone (cannot activate receptor). The liver recycles cortisone back to cortisol via 11-beta-hydroxysteroid dehydrogenase 1.
Full name and other name for IGF-1
Insulin-like growth factor 1; somatomedin C
Medullary thyroid carcinoma- presentation
Neuroendocrine carcinoma of C cells. Produces calcitonin. Most are sporadic. Hereditary associated with MEN2/FMTC.
Follicular thyroid carcinoma- genes
Gain of function mutations that activate RAS or PI-3K/AKT arm of receptor tyrosine kinase signaling pathway. PTEN loss of function (tumor suppressor) may also occur.
What type of receptor is the thyroid hormone receptor (TR)? What does it do?
Nuclear receptor. When bound, it acts as a transcription factor. Increases BMR, heat production, and O2 consumption. Increases sodium-potassium pumps, which consume ATP.
Under what pH conditions is ionized calcium increased?
Acidosis
Androgen zone (adrenal)
Zona reticularis
What is desmopressin?
Synthetic ADH (vasopressin) with modifications to reduce the effect on vasculature and increase half-life
Growth hormone insensitivity treatment
Mecasermin, a recombinant IGF-1
What is MEN2B? (Wagemann-Froboese)
Medullary thyroid carcinoma with pheochromocytoma, mucosal neuromas, ganglioneuromas, marfanoid habitus
Thyroid surgery complication causing airway obstruction (inspiratory stridor)
Bilateral recurrent laryngeal nerve injury
Action of 5/3 monodeiodinase
Clips inner iodine molecule to make reverse T3 (inactive)
How do you catch a pituitary microadenoma that is not appearing on MRI?
Inferior petrosal sinus sampling
Thyroid surgery complication causing loss of high pitch voice/projection
Superior laryngeal nerve injury
Where does cortisol have negative feedback?
It has negative feedback on corticotrophs and the hypothalamus.
What is ergocalciferol and where do you get it?
Vitamin D2; vegetables
Where is RANKL synthesized?
Osteoblasts
M2CR ligand and function
ACTH is the ligand; stimulates glucocorticoid production
How does iodine cause HYPERthyroidism?
TSH increases to compensate for inadequate T4. If there is just enough iodine to “get by,” it may cause some follicles to proliferate more than others to form a nodular goiter. Some nodules may become autonomous and secrete more thyroid hormone. This is a toxic multinodular goiter.
Blood supply to the thyroid
Superior thyroid artery (from external carotid), inferior thyroid artery (from thyrocervical trunk), thyroid ima artery (from brachiocephalic, found in 5-10% of individuals)
Differential diagnosis for painful and tender thyroiditis
Subacute (de Quervain’s/granulomatous) thyroiditis, infections thyroiditis, radiation-induced thyroiditis, trauma-induced thyroiditis
What is MEN1? (Werner’s syndrome)
Hyperparathyroidism (first), islet cell tumor, pituitary tumors. Caused by Menin on chromosome 11 (tumor suppressor). Autosomal dominant inheritance pattern; recessive mechanism (two-hit).
How do chronic granulomatous disorders cause hypercalcemia?
Activation of 1-alpha-hydroxylase
Neuroblastoma- median age
18 months
Anaplastic/undifferentiated thyroid carcinoma- genes
loss of p53 function
LH/FSH deficiency- presentation in men
Impotence, infertility, small testis, decreased muscle mass, reduced facial/body hair, thinning of skin (finely wrinkled)
What is the main function of IGF-1?
Promote organ and linear growth
What/where are the parvocellular neurons?
They originate in the paraventricular and arcuate nuclei of the hypothalamus and terminate in the median eminence. They secrete releasing hormones into the hypothalamic-hypophyseal portal vessels to act on the adenohypophysis.
Why isn’t T3 helpful in hypothyroid diagnosis?
5’/3’ deiodinase is upregulated to maitain T3 levels as normal
Pheochromocytoma- Rule of Tens
- 10% outside adrenal gland (e.g. organ of Zuckercandl)
- 10% of sporadic cases are bilateral
- 10% are malignant
- 10% do not present with HTN
Conn syndrome- diagnosis
Plasma aldosterone concentration (PAC), plasma renin activity(PRA);
PAC/PRA ratio of >20
May confirm with suppression tests (IV normal saline loading, fludrocortisone)
CT is good for masses. Bad for discerning unilateral vs. bilateral.
Adrenal vein sampling to determine side..
Superior parathyroid glands embryological origin
Fourth pharyngeal pouch
Compressive symptoms of goiter
Dyspnea (especially lying down), compression of recurrent laryngeal nerve, Horner’s syndrome, jugular vein compression
Assays to diagnose growth hormone deficiency
IGF-1 and IGFBP-3 (both decreased); GH is pulsatile and not as useful clinically
Embryological origin of the thyroid (follicular cells)
foramen cecum of the tongue (ventral diverticulum during 4th week of gestation)
Hashimoto’s thyroiditis antibody
Anti-TPO (diagnostic with symptoms but found in 20% of normal women). Anti-thyroglobulin may also be seen.
Non-metabolic effects of cortisol
Lymphocyte apoptosis, anti-inflammatory, bone health, BP regulation, CNS effects
17-alpha-hydroxylase is the same protein as what enzyme?
17,20-desmolase
Action of 5’/3’ monodeiodinase
Converts T4 to more active T3
Name for primary hyperaldosteronism
Conn syndrome
What is a sestamibi scan?
Technetium is a tracer that collects in overactive parathyroid tissue
Waterhouse-Friderichsen syndrome
Hemorrhagic adrenalitis caused by bacteremia (e.g. Neisseria meningitidis)
Normal prolactin level
2-20 ng/mL
Pheochromocytoma- treatment
- Alpha and beta adrenergic blockade
- Resection if possible
Conn syndrome- presentation
HTN, hypokalemia (1/3; may cause mild metabolic alkalosis and cramps/weakness), mild hypernatremia, higher CV mortality
Hyperprolactinemia- presentation
Hypogoadotropic hypogonadism, galactorrhea, infertility, amenorrhea/oligomenorrhea, impotence
Goiter hereditary association
MEN2A
ACTH rhythm and half-life (generally)
Circadian and pulsatile; highest in the morning and causes cortisol spike; short half-life
Papillary thyroid carcinoma- genes
Gain-of-function in growth factor receptor pathway, resulting in MAPkinase/ERK activation. RET, NTRK1 are receptor tyrosine kinases. BRAF is a serine-threonine kinase.
Usual order of hypopituitarism
Gonadotrophs (hypogonadotropic hypogonadism), then somatotrophs (dwarfism in children), then thyrotrophs (central hypothyroidism), and finally corticotrophs (secondary adrenal insufficiency)
Pituitary apoplexy- presentation
Acute onset of headache, diplopia, and hypopituitarism
Presentation, diagnosis, and treatment of follicular thyroid adenoma
Benign neoplasms that are usually nonfunctional but may produce thyroid hormone and cause thyrotoxicosis. Gain-of-function at TSH receptor. Suspected adenomas are removed for diagnostic lobectomy (fine needle aspiration is not useful).
Describe the embryological basis of the inferior parathyroid glands
Derived from third pharyngeal pouch. Descend with thymus. Reside anterior to the recurrent laryngeal nerve.
123-iodine scintigraphy- Graves’ findings
Darker appearance, elevated uptake (50-80%), ballooning lobes, prominent isthmus, pyramidal lobe seen
Propothiouracil side effects
Agranulocytosis, aplastic anemia, vasculitis, hepatitis (these side effects are rare)
What is familial medullary thyroid carcinoma (FMTC)?
Variant of MEN2 with thyroid tumor only.Must be four or more cases in a pedigree with absece of other MEN2-associated tumors.
Primary sources of cholesterol (3)
1) LDL molecules via LDL-R
2) Made from acetyl-CoA
3) Esterified cholesterol stored in lipid droplets
SIADH- presentation
Hyponatremia with low plasma osmolality, normal/high urine osmolality, absence of hypotension or hypovolemia
Prolactin level with greatest concern for prolactinoma
200 ng/mL
Hereditary conditions associated with pheochromocytoma
- MEN2
- von Hippel-Lindau
Growth hormone excess after epiphyseal plate closure
Acromegaly
Struma ovarii
Ovarian teratoma with mature thyroid tissue that secretes hormone
Normal calcium level
8.5-10.5 mg/dL
Darkest/most basophilic part of adrenal cortex on histology
Zona reticularis
Hypoaldosteronism- presentation
Metabolic acidosis with normal anion gap; typically not associated with sodium wasting. AKA type IV renal tubular acidosis.
Where are most craniopharyngiomas found?
Most from the pituitary stalk, with a minority found in the intrasellar space.
Embryological origin of parafollicular (C) cells
Ultimobranchial body (part of fourth pharyngeal pouch)
Papillary thyroid carcinoma- pathology
Psammoma bodies are microcalcifications (visible on ultrasound). Orphan-Annie nuclei have a ground glass apearance. Intranuclear grooves.
Follicular thyroid carcinoma- pathology
Tightly packed, small follicles with scant colloid. Occasional cells with abundant granular eosinophilic cytoplasm (Hurthle cell variant).
Hypoaldosteronism- treatment
Fludrocortisone
Some somatotrophs are also what type of cell?
Lactotrophs
Cushing syndrome presentation
moonface, dorsocervical fat bad, central obesity, etc.
Cretinism- cause
Hypothyroidism during fetal development. Supplementation may improve stature but not mental deficits.
Calcitonin function
Inhibits bone resorption of bone in times of stress on skeleton. May inhibit renal calcium absorption. In normal adults, little effect on serum calcium. Strong effect when bone turnover is increased (thyrotoxicosis, Paget’s)
Graves’ disease- antibody
TSH receptor antibody (TRAB), which agonizes receptor and does not let go
Enzyme that converts testosterone to DHT
5-alpha-reductase
Cortisol-cortisone shunt- purpose
Prevents large volume of cortisol from activating mineralocorticoid receptor
Time course of thyroiditis and treatment
Initially, leakage of stored thyroid hormone from colloid causes a 3-8 thyrotoxic phase, with a euthyroid phase as levels decline. The hypothyroid phase is usually asymptomatic. Recovery usually happens at 5-6 months. Beta-blockers for symptom relief.
SIADH- treatment
Fluid restriction, high solute intake/IV saline
Ghrelin promotes the secretion of which pituitary hormone?
Growth Hormone (synergistic with GHRH)
Papillary thyroid carcinoma- presentation
Best prognosis. Usually in individuals age 25-50, often with exposure to ionizing radiation. Produces thyroglobulin. Commonly spreads to lymphatics/nodes. Hypoechoic on ultrasound, and may show calcifications.
Enzyme that changes steroid from mineralocorticoid path to glucocorticoid path
17-alpha-hydroxylase
Central diabetes insipidus- treatment
Desmopressin
In what disease is a RET loss-of-function mutation observed?
Hirschsprung disease
Adrenal insufficiency- presentation
Weakness, fatigue, muscle/joint pain, hhponatremia, hypoglycemia, hyperpigmentation (sun exposed areas, due to increased ACTH and aMSH)
Craniopharyngioma- presentation
Headache, visual impairment, hormonal deficiency (growth failure)
Number of carbons in cholesterol
27
Pro-opiomelanocortin (POMC) cleavage products
ACTH and alpha-melanocyte stimulatinghormone (aMSH)
Treatment of hypercalcemia
Bisphosphonates (antiresorptive), cinacalcet (calimimetic). AVOID thiazides, lithium. In severe cases, saline loading, denosumab (RANKL inhibitor)
Name for hypersecretion of vasopressin
Syndrome of Inappropriate ADH (SIADH)
Cushing syndrome diagnosis
Overnight dexamethasone suppression test (fail to suppress cortisol), high midnight salivary cortisol, 24-hour urinary free cortisol, metyrapone test, ACTH levels
What is Laron Dwarfism?
Growth hormone insensitivity due to a mutation in the GH receptor
Empty sella (primary)- pathophysiology
Defect in the diaphragma sella allows CSF through, compressing the pituitary gland and enlarging the sella over time. Usually an asymptomatic, incidental finding.
Chief cell function in parathyroid glands
Synthesize, store, and secreate PTH
What are clinical tests for hypocalcemia?
Chvostek’s sign, Trousseau’s sign
Neuroblastoma- diagnosis
Elevated urine levels of catecholamines, metanephrines, homovanillic acid, VMA
Cortisol rhythm and half-life
Highest in the morning; long half-life
Order of enzyme actions in the zona glomerulosa
1) Cholesterol => prenenolone by cholesterol desmolase
2) Pregnenolone => progesterone by 3-beta-hydroxysteroid dehydrogenase
3) Progesterone => 11-deoxycortisone by 21-hydroxylase
4) 11-deoxycortisone-corticosterone by 11-beta-hydroxylase
5) Corticosterone => aldosterone by aldosterone synthase
Role of M3CR and M4CR
Appetite suppression; M4CR suppressed by agouti-related peptide (ghrelin pathway)
Oxyphil cell function in parathyroid glands
Who knows?
123-iodine scintigraphy- subacute/silent thyroiditis findings
Diffusely suppressed, may be patchy, uptake is very low
Causes of hyperprolactinemia
- Pregnancy
- Nipple stimulation
- Physical activity/stress
- Pituitary adenoma
- Hypothyroidism
- Exogenous estrogens
- Interfering with dopamine inhibition of lactotrophs
Where are calcium and magnesium passively reabsorbed between cells?
Thick ascending limb of the loop of Henle
Adrenal cortical adenoma- pathophysiology
Benign neoplasm of adenocortical cells that can secrete steroids independently of ACTH or RAS pathway
Glucocorticoid zone
Zona fasciculata
