Acromegaly with Non-PTH related Hypercalcemia

Raya Almazrouei, Alexander Miras, Imperial College Healthcare NHS Trust, London, UK.

Background: Hypercalcemia is rare with acromegaly and usually attributed to co-existent primary hyperparathyroidism. Patients with acromegaly frequently have mild hyperphosphatemia and hypercalciuria, while it is rarely to have overt hypercalcemia. Recent published case reports link acromegaly with hypercalcemia mediated by elevated 1,25(OH) vitamin D.

Case: We report a 33 year-old man diagnosed with acromegaly that was picked up when he presented with lower gastrointestinal bleeding with negative colonoscopy. Subsequently he reported having intermittent headache and symptoms suggestive of obstructive sleep apnoea. In addition, he witnessed marked change in the size of his feet and hands. He put on weight of around 34 kg during the last 10 years. He reported no history of kidney stones. On examination, he weighed 124 kg with BP of 174/103 and he had classic acromegaly picture with large spade like hands, which were sweaty. He had prominent periorbital ridges and zygomatics, mild prognathism, no interdental space widening or visual field loss.

Investigations (Table): showed markedly elevated GH and IGF-1 along with mildly elevated calcium that was confirmed on repeat testing a week later. The mild hypercalcemia was non PTH related as his PTH level was in the low-normal range 3.5 pmole/L.  His 24-hour calcium that was done in another day showed marked hypercalciuria of 10.24 (2.5-7.5) mmol/day. MRI pituitary confirmed adenoma of 14x20 mm in size.

Management: Three months later, the patient had trans-sphenoidal surgery with histology confirming somatotroph adenoma. Three weeks postoperatively, his bone profile showed normalization of adjusted calcium and paradoxical initial rise in PTH level with normal vitamin D level (after replacement). In October 2018 (5 months post-surgery), his labs showed normocalcemia with normal PTH and vitamin D levels. Molecular genetic sequence and MLPA analysis revealed no pathogenic variant of MEN1, AIP and CDK1B genes.

Conclusion: Despite that we did not measure the active 1,25(OH) vitamin D in this case; the sequence of bone profile is suggestive of Non-PTH mediated hypercalcemia with relatively low PTH in the first instance. Postoperatively, calcium, phosphate and PTH levels normalized.  It is likely that this occurs late in the course of active uncontrolled acromegaly as GH-IGF-1 mediate increase synthesis of 1,25(OH) vitamin D synthesis.


Initial 1st Set

Initial 2nd Set

3 weeks Post surgery

5 months Post surgery

IGF-1 (10.5-32) nmole/L





Random GH ug/L





C-calcium (2.2-2.6) mmole/L





Phosphate (0.8-1.5) mmole/L





PTH (1.6-7.2) pmole/L





25 (OH) Vitamin D (70-150) nmole/L



78.8 (after replacement)