Sx: centripetal obesity, glucose intolerance, proximal muscle weakness, HTN, hirsutism, hyperpigmentation, tinea versicolor infection Tests? Positive Urine free cortisol Identfiying Etiology? plasma ACTH=30 Cortisol suppressed with high dose dexamethasone test Dx? Tx?

Tests: 1. 24h Urine free cortisol collection: diagnostic if \>3x normal, best screening test 2. overnight low dose dexamethasone suppression test: postiive if pt does not suppress 8am cortisol to \ adrenal cushings--\>CT scan adrenals \>20pg/ml--\>pituitary or ectopic cushings between 5-20: not definitive -pituitary vs ectopic cushings: high dose dexamethasone suppression test: pts with pituitary cushings will be able to suppress ACTH secretion but ectopic will not petrosal sinus sampling: pituitary cushings will have high ACTH Dx: Pituitary Cushings' disease Tx: surgical resection

- Congenital (autosomal dominant) - Acquired: Iatrogenic (following neurosurgery) Trauma Neoplasms (pituitary tumors, craniopharyngioma….) Ischemia (Sheehan’s syndrome) Granulomas (Sarcoidosis….) Infections (Tuberculosis…) Autoimmune Idiopathic

Hypothalamus/Pituitary Flashcards by Danielle Hutchings

Pituitary development and anatomy

anterior (adenohypophysis): derived from ectoderm

posterior (neurohypophysis): derived from floor of diencephalon (hypothalamus); maintains connection to hypothalamus via pituitary stalk

located in bony sella turcica (laterally bounded by cavernous sinus, anterioinferiorly bounded by sphenoid sinus, superiorly lies optic chiasm)

vessels (hypophyseal portal system) delivers hypothalamic releasing hormones to the anterior pituitary

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pituitary Corticotropin (ACTH)

Regulated by Corticotropin-Releasing Hormone (CRH) from hypothalamus
The target organ is the adrenal glands, stimulating cortisol synthesis and secretion
Cortisol has a negative feedback on ACTH secretion (and some on CRH)
Excess leads to Cushing’s syndrome
Deficiency leads to secondary adrenal insufficiency

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Pituitary Thyroid Stimulating Hormone (TSH)

Regulated by Thyrotropin-Releasing Hormone (TRH)
The target organ is the thyroid gland, stimulating thyroid hormone synthesis and secretion
Thyroid hormones have a negative feedback on TSH secretion
Excess leads to central hyperthyroidism
Deficiency leads to central hypothyroidism

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Pituitary Growth Hormone (GH)

Regulated by Growth Hormone-Releasing Hormone (GHRH) and Somatostatin (-) from hypothalamus
The target organs are multiple tissues (bone, cartilage, muscles…..), mainly through the action of IGF1(synthesized in the liver)
IGF1 has a negative feedback on GH
Excess leads to gigantism or acromegaly
Deficiency leads to growth retardation or an adult clinical syndrome

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Pituitary Gonadotropins (LH/FSH)

LH (Luteinizing Hormone) and FSH (Follicle Stimulating Hormone)
Regulated by Gonadotropin-Releasing Hormone (GnRH) from hypothalamus
The target organs are the testes and ovaries, leading to testosterone secretion and spermatogenesis in males, as well as estradiol secretion and gametogenesis in females
Excess leads to precocious puberty
Deficiency leads to hypogonadism

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Pituitary Prolactin (PRL)

Regulated by dopamine (tonic inhibition)
The target organ is the breast (mammary glands), leading to initiation and maintenance of lactation
Excess leads to galactorrhea and amenorrhea
Deficiency leads to the inability to lactate after delivery

**only hormone under tonic inhibition!

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Posterior Pituitary ADH (vasopressin)

Regulated mainly by plasma osmolality and “effective” circulating blood volume
The target organ is the collecting tubule, leading to increase in water permeability
Excess leads to SIADH (Syndrome of Inappropriate Secretion of Antidiuretic Hormone)
Deficiency leads to central diabetes insipidus

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Posterior Pituitary Oxytocin

Regulated by neurotransmitters (cholinergic, a-adrenergic)
The target organs are:
Breasts
uterus

Role:

Milk let-down reflex
Uterine contractions during labor

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Causes of cushings syndrome:

-ACTH-dependent

ACTH-independent

Pseudo-cushings

ACTH-dependent:

cushing’s disease
ectopic ACTH
Ectopic CRH

ACTH-independent:

adrenal adenoma
adrenal carcinoma
micronodular hyperplasia
macronodular hyperplasia

Pseudo-cushings

Major depressive d/o
alcoholism

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signs and symptoms of cushing’s disease

centripetal obesity
Moon facies
buffalo hump
hirsutism
hyperpigmentation due to ACTH excess

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Sx: centripetal obesity, glucose intolerance, proximal muscle weakness, HTN, hirsutism, hyperpigmentation, tinea versicolor infection

Tests?

Positive Urine free cortisol

Identfiying Etiology?

plasma ACTH=30
Cortisol suppressed with high dose dexamethasone test

Dx?

Tx?

Tests:

24h Urine free cortisol collection: diagnostic if >3x normal, best screening test
overnight low dose dexamethasone suppression test: postiive if pt does not suppress 8am cortisol to <1.8ng/dl
salivary cortisol at midnight: positive if cortisol elevated

Etiology: determine ACTH dependency

-plasma ACTH

<5pg/ml–> adrenal cushings–>CT scan adrenals
>20pg/ml–>pituitary or ectopic cushings
between 5-20: not definitive

-pituitary vs ectopic cushings:

high dose dexamethasone suppression test: pts with pituitary cushings will be able to suppress ACTH secretion but ectopic will not
petrosal sinus sampling: pituitary cushings will have high ACTH

Dx: Pituitary Cushings’ disease

Tx: surgical resection

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Sx:  Acral enlargement / Facial changes / Heel pad thickness \> 22 mm, Prognathism / Malocclusion, Arthralgias / Carpal tunnel syndrome, Excessive sweating
 Skin tags / Greasy, oily skin, Hypertension and Diabetes
 Sleep apnea (obstructive)

Tests?

positive IGF-1
Positive OGTT

Dx?

Tx?

Tests:

IGF-1 (Somatomedin C) : high; Best screening test
Failure of GH to suppress after OGTT (Oral Glucose Tolerance Test): Gold standard test (In acromegalics, GH does not suppress to < 1 ng/ml)
If testing positive => MRI of pituitary (usually macroadenoma)

Dx: Acromegaly due to excess GH

Tx:

transphenoidal surgery (curative 50%)
if not cured by sugery use: somatostatin analog (octreotide), radiation, GH receptor antagonists
screen for colon polyps/cancer

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long term consequences of acromegaly

arthropathy
neuropathy
CV disease–cardiomyopathy
hypertension
respiratory disease–airway obstruction
malignancy–colon polyps
Carbohydrate intolerance–Diabetes, IGT

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Female Sx: amenorrhea, infertility, galactorrhea

Male Sx: decreased libido, impotence, headache/vision changes (mass effect)

Tests: abnormal pituitary MRI w/?

Dx?

Tx?

Tests: high prolactin with abnormal pituitary on MRI

Need to exclude other etiologies:

Nonfunctioning pituitary macroadenoma with compression of the stalk (will show on MRI)
Infiltrative diseases of the hypoth/pituitary axis (sarcoid, histiocytosis X etc)
Primary hypothyroidism (high prolactin)
Renal failure, Cirrhosis (can’t excrete prolactin)
Pregnancy, Stress (ammenorhic women, send for pregnancy test)
Drugs: Dopamine antagonists (mainly antipsychotics)

Dx: prolactinoma

Tx: almost always medical!

Dopamine agonists: bromocriptine (Parlodel) or cabergoline (Dostinex)
surgery reserved for pts not responding to drugs

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Thyrotrope adenoma

clinical presentation?

treatment?

-Secreting TSH
-Rare: less than 1% of all pituitary tumors
2 clinical presentations:

Hyperthyroidism with classic symptoms, goiter, high T4/T3 but inappropriately normal or elevated TSH (Remember: in primary hyperthyroidism, TSH is suppressed)
Mass effects: headache, abnormal visual fields

Treatment: Surgery

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GONADOTROPE ADENOMA

clinical presentation

treatment

Secreting FSH (most common), LH or  subunit
Frequently referred to as “nonfunctioning” adenomas
No obvious clinical endocrine syndrome from this hypersecretion

-2 clinical presentations:

Mass effects: headache, abnormal visual fields
Hypopituitarism (deficiency of other hormones from macroadenoma)

Treatment: Surgery

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Sx: polyuria/polydipsia, likes iced drinks

Tests: polyura+ urine specific gravity 1.005 or less + urine osmolality of 200mmol/l or less

Determining Etiology?

Dx: diabetes insipidus due to insufficient secretion of ADH (central) or resistance of kidney to ADH (nephrogenic)

Etiology: Central DI responds to ddAVP and nephrogenic does not

Tx:

central DI: ddAVP
nephrogenic DI: NSAIDS

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Causes of central DI

Congenital (autosomal dominant)
Acquired:
Iatrogenic (following neurosurgery)
Trauma
Neoplasms (pituitary tumors, craniopharyngioma….)
Ischemia (Sheehan’s syndrome)
Granulomas (Sarcoidosis….)
Infections (Tuberculosis…)
Autoimmune
Idiopathic

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CAUSES of NEPHROGENIC DI

Congenital (X-linked)
Acquired:
Renal disease: sickle cell disease, polycystic kidney disease, amyloidosis, obstructive uropathy…
Electrolyte disorders: hypokalemia, hypercalcemia (at level of kidney)
Drugs: lithium, demeclocycline…

hypopituitarism

Clinical syndrome resulting from the deficiency of one or multiple pituitary hormones (partial/panhypopituitarism)
GH, FSH and LH are often lost first; TSH, ACTH and ADH are usually last to be diminished, in that order
The most common cause is a pituitary macroadenoma

Sheehan’s syndrome

Results from ischemic pituitary necrosis following childbirth
It is almost always associated with severe postpartum hemorrhage and hypotension
The tip-off to its occurrence is failure to lactate postpartum

Pituitary apoplexy

def?

presentation?

work-up?

treatment>

Results from hemorrhagic infarction of a pituitary adenoma
Acute presentation with headaches, change in mental status, ophthalmoplegia and visual loss, sometimes necessitating surgical decompression (if severe)
Variable degrees of hypopituitarism

Workup should include:

MRI of the hypothalamus/pituitary
Endocrine testing: PRL, TSH & free T4, cortisol & ACTH (and if necessary, dynamic testing), testosterone in males, menstrual history in females, GH dynamic testing

Treatment depends on the etiology

May include neurosurgical intervention
Hormonal replacement

pituitary incidentalomas

- 10-20% of people (most common is pituitary microadenoma) - Need to exclude hormonal hypersecretion: PRL, IGF-1, TSH & free T4, overnight dexamethasone suppression test, LH, FSH & a-subunit - If macroadenoma =\> also need to rule out hypopituitarism (see appropriate section) and do formal visual fields testing - If all testing is normal, follow with periodic MRI (6 months, 1, 2 and 5 years)

High uptake hyperthyroidism

* Grave's disease * toxic multi-nodular goiter * toxic adenoma * TSH induced hyperthyroidism * trophoblastic disease (choriocarcinoma, hyadatiform mole secrete hCG which stimulates thyroid)

low uptake hyperthyroidism

* painful thyroiditis (subuacute, DeQuervain's) * painless thyroiditis (post-partum) * iodine induced hyperthyroidism * exogenous T3/T4 ingestion * struma ovarii * metastatic follicular carcinoma

thyroid storm

severe hyperthyroidism, fever, change in mental status

**Sx:** • Diffuse goiter w/ bruits • Opthalmopathy: o Non-infiltrative: grittiness, redness, lacrimation, lid lag, lid retraction) o Proptosis \*pathognomonic Grave’s (infiltrative) o Interferene w/ venous drainage o Extra-ocular muscle palsy (ocular nerve entrapment→blindness) • Dermopathy: o Onycholysis: retraction of nail from bed o Acropachy (clubbing)\*pathognomic Graves o Pretibial myxedema **Lab Tests:** • Elevated TSH and T3/4 • Radioisotope study: o High uptake hyperthyroidism Dx?

Dx: hyperthyroidism Grave's disease due to auto-antibodies stimulating TSH receptor

myxedema coma

hypothermia, hypoventilation, hyponatremia, depressed mental status

risk of malignancy in thyroid nodules...

- 5% to 10% incidence of overt cancer - Age: \< 20 yrs. \> 60 yrs. (10-20% ) - Sex: ♂:♀ 3:1 (nodules ♀: ♂ 4:1) - H&N XRT: Childhood XRT: 33%  in malignancy (3 yr -- peak 20 yrs) - Family history: MEN II

histology of thyroid nodule

- 70% are colloid nodules, 20% adenomas, 10% carcinomas (30% are tumors but only 10% malignant) - clinical hallmarks of malignancy: * rapid growth, * firm, fixed nodules on PE * local lymphadenopathy * distant metastases * vocal cord paralysis

Evaluating thyroid nodules

1) ultrasound: * distiguish solid vs cystic * size 2) radionuclear screening: * most nodules appear "cold" on scan; 5-10% of these are malignant * autonomously functioning nodules (independent of TSH) are hot and rarely malignant 3) FNAB: procedure of choice, perform on all nodules * benign: 70% * malignant: 5% * suspicious: 15% * insufficient: 10% Malignant and suspicious nodules should go to surgery.

evaluation of thyroid incidentalomas

• Depends on size of nodule: * \<1cm and low risk of cancer: repeat follow-up ultrasound, if enlarges FNAB (or if have initially high risk cancer) * \>1cm: requires FNAB

papillary thyroid carcinoma

70-80% of all thyroid carcinomas women , peak age in 30s mets to regional lymph nodes excellent prognosis

follicular thyroid carcinoma

20% thyroid cancer median age 50 years hematogenous spread (to lung/bone) worse prognosis than papillary

medullary thyroid carcinoma

assoc. with MEN2 syndromes 90% are sporadic tumor markers: calcitonin and CEA cannot be treated with I131

anaplastic thyroid carcinoma

rare tumor, mean age 70 aggressive, rapidly fatal

lymphoma thyroid cancer

rare assoc. w/ hashimotos thyroiditis

States leading to high Thyroid binding globulin

estrogens (OCP, pregnancy), acute or chronic hepatitis, acute intermittent porphyria, hereditary

states leading to low TBG

adrogens, glucocorticoids, nephrotic syndrome, hereditary

MEN-1

1. Pituitary adenoma 2. parathyroid hyerplasia 3. pancreatic tumors

MEN-2A

1. parathyroid hyperplasia 2. medullary thyroid carcinoma 3. pheochromocytoma

MEN-2B

1. mucosal neuromas 2. marfanoid body 3. medullary thyroid carcinoma 4. pheochromocytoma

Primary Hyperparathyroidism (PHPT) lab findings

Lab Findings: •↑ Serum Ca , ↑ PTH , ↑ Urinary Calcium

•Familial Hypocalciuric Hypercalcemia (FHH) Lab Findings:

Lab Findings: –↑ Serum Ca , ↑ PTH (not as elevated as PHPT) , ↓ Urine Calcium No surgery!