as given by Dr. Kirby

1. Pituitary and
Adrenals
ABSITE STUDY

2. Pituitary Gland
 Anterior has no direct
blood supply. There is a
portal system with blood
passing through the
posterior pituitary first
 Located in the sella turcica

3. Hypothalamus
 Releases TRH, CRH, GnRH and dopamine into median eminence
 Hypothalamus  Posterior Pituitary  Anterior Pituitary
 Dopamine inhibits prolactin secretion

4. Posterior Pituitary (neurohypohysis)
 Axons from the supraoptic and paraventricular nuclei of the hypothalamus to the
posterior pituitary
 Secretes 2 hormones
 ADH
 Release is mostly controlled by the supraoptic nuclei
 Regulated by osmolar receptors in the hypothalamus released in response to high osmolarity
 Causes increased water absorption in the renal collecting ducts
 Oxytocin
 Release is mostly controlled by the supraoptic nuclei
 Mainly functions in uterine contraction and lactation
*Posterior pituitary does NOT contain cell bodies

5. Anterior Pituitary (adenohypohysis)
 Comprises 80% of the pituitary gland mass
 Releases ACTH, TSH, GH, LH, FSH, and prolactin
 Bi-temporal hemianopia occurs from compression of CN II
by a pituitary mass at the optic chiasm
 Bromocriptine can be used to treat all endocrine secreting
pituitary tumors EXCEPT an ACTH secreting tumor
 Trans-sphenoid resection is an option, but is
contraindicated with supra-cellar extension (dumbbell-
shaped) and massive lateral extension

6. Prolactinoma
 Most common pituitary tumor (most are micro-adenomas)
 Symptoms: amenorrhea, galactorrhea, infertility, poor libido, visual problems
 Dx: Elevated prolactin (>150), MRI and visual field testing
 Tx: Most will not require surgery
 Asymptomatic AND micro (≤1cm)= follow with MRI
 Symptomatoc OR macro (>1cm)=
 Bromocryptine or cabergoline (dopamine agonist)- 85% success (safe with pregnancy)
 If failed medical Tx, hemorrhage, significant visual loss, young female wanting pregnancy, or
CSF leak then trans-sphenoid surgery- 85% success (15% recurrence)

7. Acromegaly
 Excessive GH, which stimulates secretion of IGF-1
 Most are macro-adenomas
 Symptoms: jaw enlargement, macroglossia, headaches, HTN, amenorrhea,
DM, giganticism and visual problems
 Can have cardiac issues (valvular or cardiomyopathy)
 Dx: Elevated IGF-1 (random GH is NOT useful), MRI
 Tx: Trans-sphenoid resection is first choice if no invasion to surrounding
tissue
 Octreotide and bromocriptine can shrink tumor and improve symptoms
 Pegvisomant (GH receptor antagonist)

8. Pituitary Potpourri
 Sheehan’s Syndrome
 Pituitary insufficiency in mother after delivery
 Caused by pituitary ischemia 2/2 hypovolemia/shock following childbirth
 Symptoms: Most common initial sign in difficulty with lactation; can also have amenorrhea, adrenal
insufficiency or hypothyroid
 Posterior pituitary is usually unaffected 2/2 direct blood supply
 Tx- exogenous replacement of deficiency
 Craniopharyngioma
 Most commonly occur in children 5-10yo and are benign
 Calcified cyst near anterior pituitary, remants of Rathke’s pouch (diverticulum arising from the embryonic
buccal cavity, from which the anterior pituitary gland develops)
 Symptoms: headaches, growth failure, visual problems, endocrine abnormalities, hydrocephalus
 Tx: Surgery if symptomatic (DI is a common post-op complication)
* Keep metastatic disease in mind (women with hx of breast CA and men with hx of lung CA)

9. Adrenal Anatomy
 Weighs 4-6 grams
 Arterial Supply – Inferior Phrenic, Unnamed Aorta, Renal
A. Branches
 Anterior and posterior surface are avascular
 Venous Drainage
 L Adrenal
 Drains from the lower pole into the L Renal V
 R Adrenal
 Drains the anterior surface of the gland into the posteriolateral
IVC; short
 Innervation
 Cortex= none
 Medulla= splanchnic

10. Adrenal Anatomy
 Cortex
 Originates from the mesoderm. From the adrenocortical ridge near the gonads during the 5th week
of gestation. Can have adrenal nests in the ovaries, testes or kidneys
 3 zones
 Glomerulosa (salt)– Aldosterone
 Fasciculata (sugar)– Cortisol
 Reticularis (sex)– Testosterone/estrogen
 Medulla
 Originates from the ectoderm from the neural crest
 Epinephrine (20%) – Requires PMNT – medulla or zuckerkandl (paraganglia near aortic bifrication)
 NorEpi (80%)

11. Physiology
 Renin-angiotensin-aldosterone pathway
 Decrease Na and volume stimulate renin secretion from the JXA
 Renin converts angiotensinogen to angiotensin I
 Angiotensin I is converted to angiotensin II by ACE in the lungs
 Angiotensin II then causes vasoconstriction and aldosterone secretion
 Aldosterone causes sodium retention and potassium excretion in the renal tubules
 Cortisol pathway
 Hypothalamus releases CRH
 CRH stimulates ACTH from the anterior pituitary
 ACTH stimulates cortisol synthesis and release from adrenal
 Cortisol acts in negative feedback to inhibit CRH/ACTH and also has effects on hepatic gluconeogenesis,
glycogen synthesis, protein catabolism, lipolysis
 Also causes hyperglycemia, impaired wound healing, collagen and bone loss

12. Primary Hyperaldosteronism
Conn’s Syndrome
 HTN, Hypokalemia, Polyuria, Polydipsia, Muscle Weakness
 Adenoma (60%), Bilateral Hyperplasia (40%)
 Elevated Aldosterone, Low Renin (Ratio >20:1)
 Elevated urine aldosterone following a salt loading test
 CT – adenoma vs hyperplasia
 If microadenoma (<1cm) or no mass then adrenal venous sampling to distinguish unilateral
adenoma vs B/L hyperplasia
 If macroadenoma (>1cm)- resect
 Adenoma- Resect (preop with spironolactone to normalize potassium)
 18-hydroxycorticosterone elevated (>100)with adenomas and low in hyperplasia
 Hyperplasia – Medical Tx – Spironolactone, Ca2+Blockers, Potassium

13. Hyperaldosteronism
 Secondary
 Secondary to renovascular HTN
 Elevated aldosterone AND renin
 Tertiary
 From diuretic use

14. Hypercortisolism
Cushing’s Syndrome
 Cushing’s Syndrome – Adrenal Hyperplasia, adenoma, carcinoma or ectopic ACTH or
coticotropin releasing factor (small cell carcinoma)
 Cushing’s Disease – ACTH Hypersecretion Pituitary Adenoma (60-70%)
 Weight gain, HTN, DM, Centrpetal obesity, hirsutism, striae, osteopenia
 24H Urinary/Cortisol (not serum cortisol)
 Low Dose Dexamethasone – 1mg
 Low Plasma ACTH – adrenal adenoma, hyperplasia, carcinoma
 High Plasma ACTH – Pituitary adenoma or Ectopic
 High Dose Dex – 2mg Q6h for 48H
 Etopic – Will not be suppressed
 Pituitary adenoma – Will be suppressed

15. Hypercortisolism Work-up

16. Hypercortisolism
 Source
 If adrenal suspected  CT abdomen (adrenal protocol)
 If pituitary suspected  MRI sella turcica
 If ectopic suspected  CT chest (suspected small cell carcinoma)
 Adrenalectomy
 Unilateral for adenoma or carcinoma
Need perioperative steroid coverage
 Bilateral for hyperplasia or in some cases of secondary
hypercortisolism without identification of primary tumor
Will require steroid replacement
*Exogenous steroid use is the MCC of cushingoid appearance

17. Congenital Adrenal Hyperplasia
Deficiency Aldosterone Testosterone
21-Hydroxylase Normal ↑
17-α-Hydroxylase ↑ Normal
11-α-Hydroxylase ↑ ↑
 Aldosterone
 HTN and hypokalemia
 Tertiary
 Virilization

18. Adrenal Insufficiency
 Primary – Most common is autoimmune
 Infection – Histoplasmosis, TB (MC in developing world), Meningococcus (Waterhouse Friderichsen
syndrome)
 Secondary-Iatrogenic; Exogenous Corticosteriods, most common
 Labs
 Elevated ACTH, Hyperkalemmia, Hyponatremia, Hypochloremia, Hypoglycemia, Acidosis
 Cosyntropin Stim Test – 250micrograms IV
 Cortisol level at 30-60 min if <18 is suggestive of insufficiency
 Hydrocortisone will interfere with this; can use dexamethasone
 Tx – Glucocorticoids and hydration
 Addisonian crisis
 Symptoms: hypotension, tachycardia, refractory shock
 Treat immediately. Don’t wait for labs

19. Evaluating Adrenal Mass
 Functioning or Non Functioning
 Majority are non functioning, if functioning resect regardless of size
 Blood/Urine levels – VMA, Catecholamines, Metanephrines
 Benign or Malignant
 Vast Majority are benign
 Carcinomas are rare – 50% stage IV at diagnosis
 Primary or Secondary
 Metastatic lesions from lung, breast, renal cell, melanoma, prostate, colon

20. Adrenal Incidentalomas
 Adrenal Mass discovered during imaging for unrelated reason
 DDx – Cortical adenoma, carcinoma, pheo, ganglioneuroma, cyast,
hemorrhage, fibrosis
 Evaluation
 Plasma Cortisol, Estradiol, testosterone, androstenedione
 24H urinary cortisol
 Low Dose Dexamethasone cortisol suppression test – should suppress pituitary
ACTH yielding decreased levels. No depression means cushing’s
 Renin/Aldosterone ratio
 Urinary catecholamines, metanephrines, VMA

21. Adrenal Incidentaloma
 Benign
 Round, smooth, homogenous
 Increased fat content
 Malignant
Irregular, focal hemorrhage/necrosis
 Percutaneous Bx
 Contraindicated if surgery indicated
 Perform if multiple masses present with primary unknown
 Not appropriate for hormonally active large tumor or if pheo is suspected

22. Indication for Surgery
 Hyperfunctioning – Conn, Cushing, Pheo
 Malignancy – based on CT
 Size
 Non functioning <cm 4 – Do not operate if benign imaging characteristics (smooth,
homogenous, <10 HU, >60% washout on 15min delay phase)
 CT at 3, 6, 12 months, resect if increase in size
 Non functioning 4-6cm – Individualize,
 <40yo resect, elderly observe
 Non Functioning - >6cm – Operate due to increased risk of malignancy unless clearly
benign cyst or myolipoma on imaging
 Begin metastatic workup

23. Adrenal Cortical Carcinoma
 Rare, aggressive, 60% hyperfunctioning
 Women, 40-50yo, Large (90%>6cm)
 Left sided more common
 Can present with liver mets
 Tx – Open Adrenalectomy (concern for tumor spillage), resection en bloc
 5 yr survival 20%
 No benefit to chemo/rads
 If unresectable, consider mitotane (adrenolytic agent that binds mitochondrial
proteins  adrenal atrophy and tumor death)

24. Pheochromocytoma
 Tumor of adrenal medulla or extra adrenal adrenergic tissue (neuroectodermal origin)
 Rule of 10s – 10% familial (MEN II A/B, von Hippel Lindau, Neurofibromatosis), extraadrenal
(secrete NE), multiple, bilateral, pediatric, malignant
 Sx- paroxysmal HTN, tachycardia, HTN, palpitations, flushing, sweating
 Dx – Initial plasma catecholamines/metaneprhines
 24h Urinary catecholamines (dopamine, epi, NE) and metabolites (VMA, metanephrines)
 CT abdomen
 MRI – bright T2
 Pheo Scan – MIBG I131 – concentrates in adrenergic vesicles – identify extra adrenal
 Preop – Alpha blockade first – Phenoxybenzamine (7-10d preop), then beta blockade 48 H
prior, hydrate
 If beta blockade first yields unopposed alpha yields HTN crisis
 Tx: Laparoscopic adrenalectomy

25. MEN
 MEN I
 Pituitary – Prolactinoma
 Initial Tx with bromocriptine; rare surgical excision
 Parathyroid – 4 gland hyperplasia (MC manifestation of MEN I)
 Pancreas – Neuroendocrine (MC non-functional)
 MEN IIA – Autosomal Dominant
 Medullary Thyroid Cancer (100%)
 Pheochromacytoma
 Hyperparathyroid
 MEN IIB – Autosomal Dominant
 Medullary Thyroid Carcinoma (100%)
 Pheochromacytoma
 Mucosal Neuroma/Marfanoid Habitus
Genes:
MEN I-
MEN II-
MTC-
MEN I
RET
RET, NTRK1