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posted Nov 18, 2013, 5:10 AM by Ewa Rakowski   [ updated Nov 18, 2013, 5:20 AM ]

Thanks to our RAT resident Lydia Kruge for our Monte Minute:

Last week in CRS we reviewed an interesting case about an elderly male who presented with worsening lightheadedness, frequent falls, nausea, vomiting, and a 20 lb weight loss over 2 months. Physical exam was significant for positive orthostatics and a normal neuro exam. Routine labs showed eosinophilia, and endocrine work-up revealed low TSH, FT4, ACTH, AM cortisol, prolactin, FSH, LH, and testosterone.  CT head was normal, however MRI brain showed a cystic sellar mass.  He was diagnosed with hypopituitarism secondary to this sellar mass.

Read on for a brief overview of hypopituitarism…

Presentation: The presentation of hypopituitarism can be seen as the presentation of individual anterior pituitary hormone deficiencies. Clinical presentations vary, depending on:
  1. How quickly the anterior pituitary cells are affected by disease
  2. Which anterior pituitary cells are affected (and therefore which hormones are affected)
  3. The severity of the resulting hormonal deficiencies. 
Let’s look at how a deficiency in each of the anterior pituitary hormones would present…

ACTH deficiency (secondary adrenal insufficiency):~Acute symptoms include weakness, dizziness, nausea, vomiting, and circulatory collapse.
~Chronic symptoms include fatigue, pallor, anorexia, and weight loss.
~Work-up might show hypotension, hypoglycemia, anemia, lymphocytosis, eosinophilia (cortisol stimulates apoptosis of eosinophils), and hyponatremia.
~Of note, the hyperkalemia seen in primary adrenal insufficiency is not seen, because there is no aldosterone deficiency. The hyperpigmentation seen in primary adrenal insufficiency is also not seen, because ACTH secretion is not increased.
TSH deficiency:
~Symptoms include fatigue, cold intolerance, constipation, hair loss, dry skin, and cognitive slowing.
~Work-up may reveal weight gain, bradycardia, and hypotension.
Gonadotropin (FSH, LH) deficiency:
~Results in hypogonadotropic hypogonadism (secondary hypogonadism).
~Because of ovarian hypofunction (and therefore estradiol deficiency), women may present with oligomenorrhea, loss of libido, dyspareunia, and infertility. Work-up may show osteoporosis.
~Because of testicular hypofunction (and therefore testosterone deficiency), men may present with loss of libido and infertility. Work-up may reveal decreased muscle mass, osteoporosis, and anemia.
GH deficiency:
~Symptoms include decreased muscle mass and strength, visceral obesity, fatigue, and difficult with memory and attention. Work-up may reveal dyslipidemia and premature atherosclerosis.
Prolactin deficiency:
~Inability to lactate after pregnancy.

Major Causes of hypopituitarism
Typically caused by pituitary or hypothalamic lesions:
~Disorders of the pituitary include mass lesions (pituitary adenomas, benign tumors, metastatic cancers, cysts), infiltrative lesions (lymphocytic hypophysitis, granulomatous hypophysitis, hemochromatosis), infarct (Sheehan’s syndrome), apoplexy, pituitary surgery or radiation, and genetic disorders.
~Hypothalamic disorders also include mass lesions (benign and malignant tumors) and infiltrative lesions (sarcoid, Langerhans cell histiocytosis), and disorders 2/2 radiation, trauma, or infections.
 Diagnosis: Diagnosis is made by testing for deficiencies in the individual pituitary hormones. If deficiencies are found, imaging studies should also be done to evaluate for causes of hypopituitarism.
~Corticotropin testing to evaluate for adrenal insufficiency is probably best understood by looking at a flowchart. Please note that a cosyntropin stimulation test is only required if the AM cortisol is in the ambiguous range. If the AM cortisol is <3, then you know adrenal insufficiency is present, so you need an ACTH level to differentiate between primary and secondary adrenal insufficiency. If the AM cortisol is >15 (i.e. normal), then adrenal insufficiency is ruled out.

Algorithm for the diagnosis of adrenal insufficiency (AI). The standard cosyntropin stimulation test (CST) may be used as the first-line test for evaluation of adrenal function. The CST may be unreliable in patients with new-onset (<2-4 weeks) secondary or tertiary AI. ACTH, adrenocorticotropic hormone
~Thyrotropin testing: In central hypothyroidism, expect to find low FT4 as well as low or inappropriately low TSH.
~Gonadotropin testing: In gonadotropin deficiency, expect to find inappropriately low LH and FSH. Premenopausal women will also have low estradiol, and men will have low testosterone.
~Growth Hormone testing: IGF-1 levels lower than the normal reference range is seen in GH deficiency. Provocative tests of GH secretion include insulin-induced hypoglycemia and a combination of arginine and growth hormone releasing hormone (GHRH), which result in suboptimal increases in GH if GH deficiency is present.
~Prolactin testing is not typically performed, as it can be hard to differentiate between normal and low levels of prolactin.

Treatment- Treatment involves hormone replacement, and removal of the inciting lesion if applicable.
ACTH deficiency:
~Requires replacement of cortisol, preferably with physiologic dosing (i.e. higher doses in the AM and less in the PM, to mimic the normal cortisol secretion pattern). Typical dosing is hydrocortisone 15-25mg/day divided into 2-3 doses, but prednisone or dexamethasone can also be used if compliance is an issue and longer-acting steroids are preferred.
~Remember that pts with adrenal insufficiency will need stress dose steroids in times of illness/surgery.
TSH deficiency:
~Requires replacement of thyroxine (T4) and is treated with levothyroxine, 50-200mcg/day. Dose adjustments are made by checking T4 or free T4 levels (not TSH).
~T4 should not be replaced until cortisol replacement has started, because treatment of hypothyroidism alone may result in increased metabolism of cortisol, worsening the cortisol deficiency.
LH/FSH deficiency:
~Women: If interested in fertility, they may need injectable LH/FSH for ovulation. If not interested in fertility and if not postmenopausal, then treat with estrogen/progesterone replacement.
~Men: If interested in fertility, may need injectable LH/FSH for spermatogenesis. Otherwise, testosterone can be replaced.
GH deficiency:
-Patients can receive recombinant human GH, based on IGF-1 levels.

Back to the case
Our CRS patient was started on hydrocortisone, then levothyroxine. He was evaluated by neurosurgery and planned for outpatient surgical resection of his sellar mass.

For further details regarding this interesting topic, please see the attached Lancet review article on hypopituitarism.
Ewa Rakowski,
Nov 18, 2013, 5:17 AM