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Anterior Hypopituitarism

Opioid use disorder has become a common cause of functional hypopituitarism.

About 63% of long-term opioid (including methadone) users develop partial hypogonadotropic hypogonadism.

Opioid use also causes secondary adrenal insufficiency in about 15% of patients but is less likely to cause growth hormone or thyroid deficiency.

Thyroid Cancer

In patients with BRAFV600E mutant anaplastic thyroid cancer, combined BRAF and MEK inhibition with dabrafenib and trametinib has induced durable responses.


Doses of vitamin D3 above 4000 international units daily in adults are generally not advised (except in patients with intestinal malabsorption), since gastrointestinal side effects or hypercalcemia may occur.

Vitamin D should not be taken with topical calcipotriene to avoid hypercalcemia.

The effects of denosumab on bone wane quickly after 6 months and patients can experience a dramatic increased risk of multiple vertebral fractures within 1–2 years following discontinuation of denosumab.

Therefore, denosumab must be given on-schedule without drug holidays.

Denosumab should not be discontinued without substituting another anti-resorptive agent (bisphosphonate, estradiol, or SERM) or other therapy.

Rickets & Osteomalacia

Patients with high FGF-23 levels can have genetic testing for X-linked hypophosphatemic rickets (PHEX), autosomal dominant hypophosphatemic rickets (FGF23), and autosomal recessive hypophosphatemic rickets (DMP1).

In hypophosphatemic patients without such mutations, searching for a tumor causing tumor-induced osteomalacia is reasonable, particularly in patients with bone pain or fractures.

Such tumors are typically small and may be located anywhere, so they are best localized using a whole-body DOTATATE-PET/CT scan.

For patients with tumoral hypophosphatemia, resection of the tumor normalizes serum phosphate levels, but about 20% experience recurrence, usually in the same location.

With both tumoral and genetic FGF-23-related hypophosphatemia, therapy with burosumab improves osteomalacia.

For patients who cannot take burosumab or who continue to have hypophosphatemia, oral phosphate supplements must be given long-term; oral phosphate causes diarrhea at higher doses, however, so many patients do not achieve normal serum phosphate levels. Calcitriol, 0.25–0.5 mcg daily is given to improve the impaired calcium absorption caused by the oral phosphate.

Patients with hypophosphatasia may be treated with asfotase alfa (Strensiq). Teriparatide can improve bone pain and fracture healing. Bisphosphonates are contraindicated.

Male Hypogonadism

An oral preparation of testosterone undeconoate (Jatenzo) is available in capsules of 158 mg, 198 mg, and 237 mg and should be taken with food.

Serum testosterone falls to low levels by 12 hours after an oral dose; dosing every 8 hours may produce more consistent serum testosterone levels.

Testosterone replacement has not been considered to significantly increase ...

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