Panhypopituitarism

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Diagnosis and reasoning

At a first glance, this patient has presented with a collection of vague and nonspecific symptoms, and a battery of investigations that are completely normal, except for borderline serum sodium levels. However, his examination provides a valuable clue: the scant pubic, axillary, and facial hair raise suspicion of an endocrine etiology. An endocrine profile reveals low hormone levels across the board, save for prolactin, which is elevated. The decreased levels of stimulatory hormones (ACTH, TSH, FSH, and LH) suggest at hypopituitarism, i.e. a partial or complete deficiency of anterior pituitary hormones. Given the absence of cranial trauma, surgery, or radiotherapy, a tumor is high on the list of etiological possibilities. Hence, imaging of the brain is indicated, with MRI being the investigation of choice. This reveals a heterogeneous soft tissue lesion in the parasellar region compressing the pituitary stalk. A prolactinoma is clinically less likely here, as these are typically associated with prolactin levels >200 ng/mL. The slightly elevated prolactin levels seen here are more probably due to compression of the pituitary stalk; the resulting impairment of dopamine delivery to the pituitary causes disinhibition of prolactin secretion. An ACTH stimulation test is probably unnecessary, given the ample supporting evidence for secondary (i.e. pituitary) adrenal insufficiency. A skeletal survey is also of dubious value. Urgent neurosurgical referral is essential. Unfortunately, even after tumor resection, he is likely to require some degree of hormone replacement. Note that his adrenal insufficiency must be treated before the hypothyroidism; the opposite order may result in circulatory collapse. As growth hormone levels are normal, there is no justification for starting replacement therapy.


Discussion

"Panhypopituitarism" refers to the partial or complete insufficiency of all anterior pituitary hormones. This is a rare disorder, with less than 200,000 people in the USA estimated to be affected; however, given the variable and often vague presentation, the above number is possibly an underestimation. Key causes of panhypopituitarism include pituitary tumors, intracranial surgery, and cranial irradiation. Other causes include infiltrative diseases and vascular events (for example, pituitary apoplexy). The clinical manifestations range from nonspecific weakness and lethargy to sudden collapse and death, depending on the rapidity of onset of the disease, type and number of pituitary cells affected, and severity of hormonal deficiencies. Growth hormone (GH) deficiency usually manifests first; patients may complain of lethargy and generalized weakness, and demonstrate decreased muscle mass and strength, increased central adiposity, dyslipidemia, and reduced bone mineral density. Follicle-stimulating hormone (FSH) and luteinizing hormone (LH) deficiency typically presents as amenorrhea, atrophic vaginitis, infertility, hot flushes and breast atrophy in females, and testicular atrophy, erectile dysfunction, and decreased libido in males. Adrenocorticotropic hormone (ACTH) deficiency manifests as weakness, abdominal pain, weight loss, hypoglycemia, nausea, vomiting, anorexia, and postural hypotension. Note that if the ACTH loss is very acute, rapid hypocortisolism can lead to sudden vascular collapse and death. Thyroid stimulating hormone (TSH) deficiency leads to weight gain, cold intolerance, constipation, dry skin, non-pitting edema, slow reflexes, and bradycardia. Prolactin deficiency is asymptomatic unless the patient is a lactating mother. In addition to the above, signs and symptoms specific to the underlying etiology may also be present, e.g. headaches, diplopia, and bilateral visual defects in the case of a pituitary tumor. The diagnosis is based on demonstration of low levels of pituitary hormones and target hormones. Low thyroxine levels with low or normal TSH levels, an undetectable or low early morning cortisol level with a low or normal serum ACTH, and inappropriately low or normal levels of gonadotropins with low levels of sex hormones are typically seen. Where GH deficiency is suspected, a stimulatory test is required to assess growth hormone reserve; the insulin tolerance test (ITT) is the most commonly used test in this respect. Imaging of the hypothalamic-pituitary region is necessary to rule out peripituitary tumors, with MRI being preferred. The management includes patient education, treatment of the underlying cause, and hormone replacement therapy. In particular, these individuals should be instructed about the effects of the disease on their routine life, the prognosis, and the need to adjust medication dosages during illness, surgery or any other physical or emotional stress. Hormone replacement therapy is geared at replacing target hormones, rather than the deficient pituitary hormones. The aim is to achieve normal target hormone levels, so as to restore physiology. Importantly, adrenal insufficiency must always be treated before hypothyroidism. Treating the hypothyroidism first may increase the clearance of the little cortisol that is produced, thereby precipitating an acute collapse. Prompt diagnosis and initiation of hormone replacement therapy can improve survival and quality of life. Lifelong follow up is required to avoid over- or under-treatment and for adequate management during stressful situations. Unfortunately, patient adherence to therapy is low, possibly due to the long time intervals involved.


Take home messages

  1. Panhypopituitarism refers to the partial or complete insufficiency of all anterior pituitary hormones; the spectrum of presentation ranges from nonspecific weakness and lethargy, to sudden collapse and death.
  2. The key aspects of the management are patient education, treatment of the underlying cause, and hormone replacement therapy.
  3. Hormone replacement therapy is geared at replacing target hormones, rather than the deficient pituitary hormones.

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