Summary

Tumour-induced osteomalacia (TIO) is due to an overproduction of fibroblast growth factor 23 (FGF23) by mesenchymal tumours, causing hypophosphatemia, osteomalacia and muscle weakness. TIO is usually cured by tumour resection, but neoplasms may be unidentifiable and unresectable or the patient may refuse surgery. In these cases, medical treatment with oral phosphate and calcitriol is mandatory, but it is not fully effective and it is associated with low compliance. Burosumab, a human MAB against FGF23 employed to treat X-linked hypophosphatemia (XLH), has recently been approved for TIO in the USA. Maximum burosumab dose in XLH is 90 mg administered for 2 weeks; there are no data on clinical efficacy and safety of this dose in TIO. We reported the case of a 73 years old male with multiple non-traumatic fractures, low bone mineral density, pain and reduced independence of activities of daily living. Biochemical evaluation showed hypophosphatemia, high alkaline phosphatase (ALP) and C-terminal telopeptide (CTX) and normal albumin-corrected total calcium and parathyroid hormone. Tubular phosphate reabsorption was low (80%), whereas C-terminal tail of FGF23 (cFGF23) was elevated. A ⁶⁸Ga-DOTATOC PET was performed, identifying a lesion in the first left rib. The patient refused surgery; therefore, burosumab therapy was started. After 18 months of treatment (maximum dose: 60 mg administered for 2 weeks), plasma phosphate normalized and ALP levels improved (138 U/L). Patient clinical symptoms as well as pain severity and fatigue improved. Neither adverse events nor tumour progression was reported during follow-up except for a painless fracture of the second right rib.

Learning points

• Our case shows efficacy and safety of burosumab treatment administered every 2 weeks in a tumour-induced osteomalacia (TIO) patient.

• After 18 months of treatment at a maximum dose of 60 mg every 2 weeks, we found plasma phosphate normalization and ALP reduction as well as improvement in clinical symptoms and fatigue.

• Neither adverse events nor tumour progression was reported during follow-up, except for a painless fracture of the second right rib.

Summary

Cushing’s disease or pituitary adrenocorticotropic hormone (ACTH)-dependent Cushing’s syndrome is considered a rare condition. It is caused by hypersecretion of the ACTH by a pituitary adenoma that ultimately induces endogenous hypercortisolism by stimulating the adrenal glands. It is responsible for significant morbidity and mortality. The clinical signs and symptoms of hypercortisolism are usually common and non-specific including obesity, moon face, hypertension, hirsutism and facial plethora. The association between Cushing’s disease and calcinosis cutis which is defined as dystrophic calcium deposition in the skin and subcutaneous tissues is extremely rare. To the best of our knowledge, it has never been described previously in humans, probably like a symptom or complication of chronic and severe hypercortisolism. In this paper, we report a case of a 30-year-old female diagnosed with Cushing’s disease and presented bilateral leg’s calcinosis cutis complicated with ulceration. The evolution was favorable and the complete cicatrization was obtained 12 months following the suppression of systemic glucocorticoid excess.

Learning points

• Calcinosis cutis is common in autoimmune connective diseases. However, to our knowledge, it has never been reported in humans with Cushing’s disease.

• Given the rarity of this association, the diagnostic approach to calcinosis cutis must exclude the other etiologies.

• Calcinosis cutis is challenging to treat with no gold standard therapy. In our case, the use of the combination of colchicine and bisphosphonates does not significantly improve the patient’s outcomes. In fact, we suppose that without treating the endogenous hypercortisolism, the calcinosis cutis will not resolve.

Summary

Hypercalcaemia is a very common endocrine condition, yet severe hypercalcaemia as a result of fungal infection is rarely described. There are have only been two reported cases in the literature of hypercalcaemia associated with Cryptococcus infection. Although the mechanism of hypercalcaemia in these infections is not clear, it has been suggested that it could be driven by the extra-renal production of 1-alpha-hydroxylase by macrophages in granulomas. We describe the case of a 55-year-old woman with a 1,25-OH D-mediated refractory hypercalcaemia in the context of a Cryptococcus neoformans infection. She required treatment with antifungals, pamidronate, calcitonin, denosumab and high-dose glucocorticoids. A disseminated fungal infection should be suspected in immunosuppressed individuals presenting with hypercalcaemia.

Learning point

• In immunocompromised patients with unexplained hypercalcaemia, fungal infections should be considered as the differential diagnoses;

• Glucocorticoids may be considered to treat 1,25-OH D-driven hypercalcaemia; however, the benefits of lowering the calcium need to be balanced against the risk of exacerbating an underlying infection;

• Fluconazole might be an effective therapy for both treatment of the hypercalcaemia by lowering 1,25-OH D levels as well as of the fungal infection.

Summary

An 82-year-old female was admitted to a general hospital due to progressive bilateral lower limb weakness. A T8–T9 extramedullary meningioma was diagnosed by MRI, and the patient was referred for excision of the tumour. During the patient’s admission, she was noted to have persistent hyperkalaemia which was refractory to treatment. Following a review by an endocrinology team, a diagnosis of pseudohyperkalaemia secondary to thrombocytosis was made. This case demonstrates the importance of promptly identifying patients who are susceptible to pseudohyperkalaemia, in order to prevent its potentially serious consequences.

Learning points

• Pseudohyperkalaemia should be considered in patients with unexplained or asymptomatic hyperkalaemia. It should also be considered in those patients who are resistant to the classical treatment of hyperkalaemia.

• A diagnosis of pseudohyperkalaemia is considered when there is a difference of >0.4 mmol/L of potassium between serum and plasma potassium in the absence of symptoms and ECG changes.

• In patients who are presenting with consistently elevated serum potassium levels, it may be beneficial to take venous blood gas and/ or plasma potassium levels to rule out pseudohyperkalaemia.

• Pseudohyperkalaemia may subject patients to iatrogenic hypokalaemia which can be potentially fatal.

• Pseudohyperkalaemia can occur secondary to thrombocytosis, red cell haemolysis due to improper blood letting techniques, leukaemia and lymphoma.

Summary

Primary hyperparathyroidism requires a surgical approach to achieve a long-term cure. However, post-surgical recurrence significantly complicates the management of this condition. A number of causes for recurrent disease are well understood and several diagnostic modalities exist to localise the culprit parathyroid adenoma although none of them is efficacious in localisation of the recurrent lesion. In this case report, we highlight a novel causative mechanism and describe a unique diagnostic sequence that enabled curative treatment to be delivered.

Learning points

• In the case described herein, we describe a novel location for a parathyroid adenoma causing recurrent PHPT. The case elucidates well the difficulties presented by such cases in terms of surgical planning and show the utility of PVS in such cases. Based on this case, we make the following recommendations:

• Meticulous care must be taken to prevent seeding of adenomatous tissue during primary excision.

• To consider the use of PVS in patients with discordant imaging in the setting of recurrent/persistent PHPT as a method to localise the causative adenoma.

• Same day PVS and surgery is a viable option for patients who either represent an anaesthetic risk or who are extremely anxious about the prospect of two separate procedures.

• Disordered calcium homeostasis is an important but forgotten cause of dysphagia which can be extremely debilitating for affected patients.

Summary

Ammonium acid urate (AAU) crystals are rare in industrialized countries. Furthermore, the number of children with diabetic ketoacidosis (DKA) who develop severe acute kidney injury (AKI) after hospitalization is small. We encountered two patients with AKI caused by AAU crystals during the recovery phase of DKA upon admission. They were diagnosed with severe DKA and hyperuricemia. Their urine volume decreased and AKI developed several days after hospitalization; however, acidosis improved in both patients. Urine sediment analysis revealed AAU crystals. They were treated with urine alkalization and diuretics. Excretion of ammonia in the urine and urine pH levels increased after treatment of DKA, which resulted in the formation of AAU crystals. In patients with severe DKA, the urine and urine sediment should be carefully examined as AAU can form in the recovery phase of DKA.

Learning points:

• Ammonium acid urate crystals could be formed in the recovery phase of diabetic ketoacidosis.

• Diabetic ketoacidosis patients may develop acute kidney injury caused by ammonium acid urate crystals.

• Urine and urine sediment should be carefully checked in patients with severe DKA who present with hyperuricemia and volume depletion.

Summary

Conventional treatment of hypoparathyroidism relies on oral calcium and calcitriol. Challenges in managing post-parathyroid- and post-thyroidectomy hypocalcaemia in patients with a history of bariatric surgery and malabsorption have been described, but postoperative management of bariatric surgery in patients with established hypoparathyroidism has not. We report the case of a 46-year-old woman who underwent elective sleeve gastrectomy on a background of post-surgical hypoparathyroidism and hypothyroidism. Multiple gastric perforations necessitated an emergency Roux-en-Y gastric bypass. She was transferred to a tertiary ICU and remained nil orally for 4 days, whereupon her ionised calcium level was 0.78 mmol/L (1.11–1.28 mmol/L). Continuous intravenous calcium infusion was required. She remained nil orally for 6 months due to abdominal sepsis and the need for multiple debridements. Intravenous calcium gluconate 4.4 mmol 8 hourly was continued and intravenous calcitriol twice weekly was added. Euthyroidism was achieved with intravenous levothyroxine. Maintaining normocalcaemia was fraught with difficulties in a patient with pre-existing surgical hypoparathyroidism, where oral replacement was impossible. The challenges in managing hypoparathyroidism in the setting of impaired enteral absorption are discussed with analysis of the cost and availability of parenteral treatments.

Learning points:

• Management of hypoparathyroidism is complicated when gastrointestinal absorption is impaired.

• Careful consideration should be given before bariatric surgery in patients with pre-existing hypoparathyroidism, due to potential difficulty in managing hypocalcaemia, which is exacerbated when complications occur.

• While oral treatment of hypoparathyroidism is cheap and relatively simple, available parenteral options can carry significant cost and necessitate a more complicated dosing schedule.

• International guidelines for the management of hypoparathyroidism recommend the use of PTH analogues where large doses of calcium and calcitriol are required, including in gastrointestinal disorders with malabsorption.

• Approval of subcutaneous recombinant PTH for hypoparathyroidism in Australia will alter future management.

Summary

Standard treatment of hypoparathyroidism consists of supplementation of calcium and vitamin D analogues, which does not fully restore calcium homeostasis. In some patients, hypoparathyroidism is refractory to standard treatment with persistent low serum calcium levels and associated clinical complications. Here, we report on three patients (58-year-old male, 52-year-old female, and 48-year-old female) suffering from severe treatment-refractory postsurgical hypoparathyroidism. Two patients had persistent hypocalcemia despite oral treatment with up to 4 µg calcitriol and up to 4 g calcium per day necessitating additional i.v. administration of calcium gluconate 2–3 times per week, whereas the third patient presented with high frequencies of hypocalcemic and treatment-associated hypercalcemic episodes. S.c. administration of rhPTH (1–34) twice daily (40 µg/day) or rhPTH (1–84) (100 µg/day) only temporarily increased serum calcium levels but did not lead to long-term stabilization. In all three cases, treatment with rhPTH (1–34) as continuous s.c. infusion via insulin pump was initiated. Normalization of serum calcium and serum phosphate levels was observed within 1 week at daily 1–34 parathyroid hormone doses of 15 µg to 29.4 µg. Oral vitamin D and calcium treatment could be stopped or reduced and regular i.v. calcium administration was no more necessary. Ongoing efficacy of this treatment has been documented for up to 7 years so far. Therefore, we conclude that hypoparathyroidism that is refractory to both conventional treatment and s.c. parathyroid hormone (single or twice daily) may be successfully treated with continuous parathyroid hormone administration via insulin pump.

Learning points:

• Standard treatment of hypoparathyroidism still consists of administration of calcium and active vitamin D.

• Very few patients with hypoparathyroidism also do not respond sufficiently to standard treatment or administration of s.c. parathyroid hormone once or twice daily.

• In those cases, continuous s.c. administration of parathyroid hormone via insulin pump may represent a successful treatment alternative.

Summary

We report the case of a 65-year-old female who presented with symptomatic hypercalcaemia (corrected calcium of 4.57 mmol/L) with confusion, myalgias and abdominal discomfort. She had a concomitant metabolic alkalosis (pH 7.46, HCO₃ ^- 40 mmol/L, pCO₂ 54.6 mmHg). A history of significant Quick-Eze use (a calcium carbonate based antacid) for abdominal discomfort, for 2 weeks prior to presentation, suggested a diagnosis of milk-alkali syndrome (MAS). Further investigations did not demonstrate malignancy or primary hyperparathyroidism. Following management with i.v. fluid rehydration and a single dose of i.v. bisphosphonate, she developed symptomatic hypocalcaemia requiring oral and parenteral calcium replacement. She was discharged from the hospital with stable biochemistry on follow-up. This case demonstrates the importance of a detailed history in the diagnosis of severe hypercalcaemia, with MAS representing the third most common cause of hypercalcaemia. We discuss its pathophysiology and clinical importance, which can often present with severe hypercalcaemia that can respond precipitously to calcium-lowering therapy.

Learning points:

• Milk-alkali syndrome is an often unrecognised cause for hypercalcaemia, but is the third most common cause of admission for hypercalcaemia.

• Calcium ingestion leading to MAS can occur at intakes as low as 1.0–1.5 g per day in those with risk factors.

• Early recognition of this syndrome can avoid the use of calcium-lowering therapy such as bisphosphonates which can precipitate hypocalcaemia.

Learning points

• FHH is an important differential diagnosis for hypercalcaemia.

• FHH can rarely cause pancreatitis.

• No clear strategy is available to help in the management of patients with pancreatitis due to FHH.

• Cinacalcet was effective in lowering serum calcium levels and reducing the frequency of pancreatitis in our patient with FHH.