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Summary
Calciphylaxis is a rare disorder characterised by the development of painful necrotic skin lesions. Occlusion of cutaneous arterioles due to ectopic calcification leads to potentially life-threatening widespread skin loss. Most cases occur in patients with chronic renal disease, which leads to dysregulation of calcium and phosphate homeostasis. Only a handful of case reports exist describing calciphylaxis occurring in patients without chronic renal disease but with hypoparathyroidism. We report on a unique case of a 53-year-old man with multiple endocrine neoplasia type 1 syndrome and acquired hypoparathyroidism due to total parathyroidectomy who went on to develop calciphylaxis following cardiac surgery.
Learning points
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Calciphylaxis most commonly occurs in the context of chronic renal disease but can rarely occur in its absence as a consequence of calcium and phosphate dysregulation.
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Patients who develop necrotic skin lesions in the presence of hypoparathyroidism require an urgent dermatological opinion.
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Mortality from calciphylaxis is high, with the majority of deaths occurring secondary to sepsis.
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Management of calciphylaxis requires a multidisciplinary team approach to manage wound healing, infections and pain.
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Recovery with full rehabilitation from calciphylaxis can take months to years.
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Summary
Primary hyperparathyroidism most commonly presents with hypercalcaemia. Rarely, parathyroid apoplexy or haemorrhage mimicking a thyroid bleeding cyst is the first presentation of a parathyroid adenoma. A woman presented with a sudden-onset painful ‘goitre’. Ultrasound showed a cystic nodule located posterior to rather than in the right thyroid lobe, suggesting parathyroid adenoma bleeding. Biochemistry showed mild primary hyperparathyroidism. 99mTc-pertechnetate/sestamibi showed no uptake in the nodule, which was interpreted as a cold thyroid nodule. 18F-fluorocholine PET/CT showed uptake in the nodule, suggestive of a parathyroid adenoma. Persistent mild primary hyperparathyroidism complicated by nephrolithiasis and osteopenia favoured parathyroidectomy over a wait-and-see approach. The patient was referred for parathyroidectomy along with right thyroid lobectomy. Pathology showed an adenoma, with an eccentrically located cystic structure filled with red blood cells surrounded by a thickened fibrous capsule. In conclusion, cervical pain/haemorrhage with hypercalcaemia points to the diagnosis of parathyroid apoplexy, mimicking a thyroid bleeding cyst. Workup with ultrasound and, if available, 18F-choline PET/CT allows for timely surgery, minimizing the risk of recurrent and severe bleeding.
Learning points
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A bleeding cyst may be located posterior to rather than in the thyroid, suggesting a parathyroid haemorrhage.
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Neck pain and/or haemorrhage along with primary hyperparathyroidism point to parathyroid apoplexy.
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A two-step presentation has been described, with a first phase of local symptoms to be followed by visible and possibly life-threatening compressing bleeding.
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Therefore, an expedited workup is needed, allowing for timely surgery.
Search for other papers by Ekaterina Kim in
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Summary
A 59-year-old male presented with an accidental thyroid mass in 2022. Ultrasound and CT scan showed a nodule 5.2 × 4.9 × 2.8 cm (EU-TIRADS 4) in the right lobe of the thyroid gland. Taking into account the results of the fine needle aspiration biopsy (Bethesda V), intrathyroid localization, and absence of clinical symptoms, a malignant tumor of the thyroid gland was suspected. The patient underwent total thyroidectomy using fluorescence angiography with indocyanine green, and two pairs of intact parathyroid glands were visualized in typical localization. Unexpected histological and immunohistochemistry examinations revealed parathyroid carcinoma. Due to the asymptomatic course of the disease and atypical localization of parathyroid tumor, primary hyperparathyroidism was not suspected before the surgery. The diagnosis of asymptomatic intrathyroid parathyroid cancer is a serious diagnostic challenge for a wide range of specialists.
Learning points
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Parathyroid cancer is a rare disease that may be asymptomatic.
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Intrathyroidal localization of parathyroid carcinoma is casuistic and challenging for diagnosis, and the treatment strategy is not well defined.
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Preoperative parathyroid hormone and serum calcium testing are recommended for patients with solid thyroid nodules (Bethesda IV–V).
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Search for other papers by Natalie E Cusano in
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Summary
We present the first report of use of recombinant human parathyroid hormone (1-84) (rhPTH(1-84)) in a hypoparathyroid patient during early pregnancy and lactation. The patient developed postoperative hypoparathyroidism as a 28-year-old woman following total thyroidectomy for multinodular goiter. She was not well controlled with conventional therapy, and started rhPTH(1-84) in 2015 following its approval in the United States. She became pregnant in 2018 at age 40. She discontinued rhPTH(1-84) therapy at 5 weeks gestation but resumed in the postpartum period while breastfeeding. Her daughter’s serum calcium was borderline elevated at 8 days postpartum but within the normal range at 8 weeks postpartum. The patient stopped nursing at around 6 months postpartum. Her daughter is now at 4 years and 5 months of age and is healthy and meeting developmental milestones. She was again pregnant at 8 months postpartum from her first pregnancy, and she made an informed decision to continue parathyroid hormone. At 15 weeks gestation, rhPTH(1-84) was recalled in the United States due to issues with the delivery device, and she discontinued rhPTH(1-84) treatment and resumed calcium and calcitriol supplements. She gave birth to a baby boy at 39 weeks in January 2020. At 3 years and 2 months of age, he is overall healthy. Further data are needed regarding the safety of rhPTH(1-84) in pregnancy and lactation.
Learning points
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rhPTH(1-84) is approved for therapy of patients with hypoparathyroidism; however, there are no data regarding the safety of treatment during nursing and pregnancy.
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There are multiple alterations in mineral metabolism during normal pregnancy and lactation.
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Summary
Primary hyperparathyroidism (PHP) is the most common aetiology for hypercalcaemia. The incidence of PHP in pregnant women is reported to be 8/100 000 population/year. It presents a threat to the health of both mother (hyperemesis, nephrolithiasis) and fetus (fetal death, congenital malformations, and neonatal severe hypocalcaemia-induced tetany). However, there is a lack of clear guidance on the management of primary hyperparathyroidism in pregnancy. In this study, we describe the case of a 26-year-old female patient who presented with severe hypercalcaemia secondary to PHP and underwent successful parathyroid adenectomy under local anaesthesia.
Learning points
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Primary hyperparathyroidism is a rare complication in pregnancy, but the consequences for mother and fetus can be severe.
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A perceived risk of general anaesthesia to the fetus in the first trimester has resulted in a general consensus to delay parathyroid surgery to the second trimester when possible – although the increased risk of fetal loss may occur before planned surgery.
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If the patient presents with severe or symptomatic hypercalcaemia, minimally invasive surgery under local anaesthetic should be considered regardless of the gestational age of the pregnancy.
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Summary
Milk–alkali syndrome (MAS) is a triad of hypercalcaemia, metabolic alkalosis and renal insufficiency. In this study, we present a case of milk–alkali syndrome secondary to concurrent use of over-the-counter (OTC) calcium carbonate-containing antacid tablets (Rennie®) for dyspepsia and calcium carbonate with vitamin D3 (Adcal D3) for osteoporosis. A 72-year-old woman presented with a 2-day history of nausea, vomiting, epigastric pain, constipation, lethargy and mild delirium. Past medical history included osteoporosis treated with daily Adcal D3. Initial blood tests showed elevated serum-adjusted calcium of 3.77 mmol/L (normal range, 2.2–2.6) and creatinine of 292 µmol/L (45–84) from a baseline of 84. This was corrected with i.v. pamidronate and i.v. fluids. She developed asymptomatic hypocalcaemia and rebound hyperparathyroidism. Myeloma screen, vasculitis screen and serum angiotensin-converting enzyme (ACE) were normal, while the CT of the chest, abdomen and pelvis showed renal stones but no malignancy. A bone marrow biopsy showed no evidence of malignancy. Once the delirium resolved, we established that prior to admission, she had been excessively self-medicating with over-the-counter antacids (Rennie®) as required for epigastric pain. The increasing use of calcium preparations for the management of osteoporosis in addition to easily available OTC dyspepsia preparations has made MAS the third most common cause of hypercalcaemia hospitalisations. Educating patients and healthcare professionals on the risks associated with these seemingly safe medications is required. Appropriate warning labels on both calcium preparations used in the management of osteoporosis and OTC calcium-containing preparations would prevent further similar cases and unnecessary morbidity and hospital admission.
Learning points
What is known?
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An association between high-dose calcium supplementation and hypercalcaemia crisis has been seen in case studies.
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After as little as 1 week of excessive calcium carbonate ingestion, patients can present with symptomatic hypercalcemia, acute renal failure and metabolic alkalosis (1).
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Women aged 50 and younger need 1 g of calcium per day, while aged 51 and older need 1.2 g (1).
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Although the amount of calcium required for MAS is generally thought to be more than 4 g per day, there have been reports at intakes as low as 1.0–1.5 g per day in pre-existing risk factors including renal impairment (2).
What this study adds?
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The danger of excessive ingestion of antacid is not adequately highlighted to prescribers and patients.
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Appropriate warning labels on OTC calcium-containing preparations could prevent unnecessary morbidity and hospital admission.
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Division of Cancer Studies, King’s College London, London, UK
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Faculty of Life Sciences and Medicine, School of Life Course Sciences, King’s College London, London, UK
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Barts and the London School of Medicine, Centre for Endocrinology, William Harvey Institute, London, UK
Neuroendocrine Tumour Unit, Royal Free Hospital, London, UK
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Obesity, Type 2 Diabetes and Immunometabolism Research Group, Department of Diabetes, Faculty of Life Sciences, School of Life Course Sciences, King’s College London, London, UK
Division of Reproductive Health, Warwick Medical School, University of Warwick, Coventry, UK
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Summary
A 49-year-old teacher presented to his general physician with lethargy and lower limb weakness. He had noticed polydipsia, polyuria, and had experienced weight loss, albeit with an increase in central adiposity. He had no concomitant illnesses and took no regular medications. He had hypercalcaemia (adjusted calcium: 3.34 mmol/L) with hyperparathyroidism (parathyroid hormone: 356 ng/L) and hypokalaemia (K: 2.7 mmol/L) and was admitted for i.v. potassium replacement. A contrast-enhanced CT chest/abdomen/pelvis scan revealed a well-encapsulated anterior mediastinal mass measuring 17 × 11 cm with central necrosis, compressing rather than invading adjacent structures. A neck ultrasound revealed a 2 cm right inferior parathyroid lesion. On review of CT imaging, the adrenals appeared normal, but a pancreatic lesion was noted adjacent to the uncinate process. His serum cortisol was 2612 nmol/L, and adrenocorticotrophic hormone was elevated at 67 ng/L, followed by inadequate cortisol suppression to 575 nmol/L from an overnight dexamethasone suppression test. His pituitary MRI was normal, with unremarkable remaining anterior pituitary biochemistry. His admission was further complicated by increased urine output to 10 L/24 h and despite three precipitating factors for the development of diabetes insipidus including hypercalcaemia, hypokalaemia, and hypercortisolaemia, due to academic interest, a water deprivation test was conducted. An 18flurodeoxyglucose-PET (FDG-PET) scan demonstrated high avidity of the mediastinal mass with additionally active bilateral superior mediastinal nodes. The pancreatic lesion was not FDG avid. On 68Ga DOTATE-PET scan, the mediastinal mass was moderately avid, and the 32 mm pancreatic uncinate process mass showed significant uptake. Genetic testing confirmed multiple endocrine neoplasia type 1.
Learning points
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In young patients presenting with primary hyperparathyroidism, clinicians should be alerted to the possibility of other underlying endocrinopathies.
In patients with multiple endocrine neoplasia type 1 (MEN-1) and ectopic adrenocorticotrophic hormone syndrome (EAS), clinicians should be alerted to the possibility of this originating from a neoplasm above or below the diaphragm.
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Although relatively rare compared with sporadic cases, thymic carcinoids secondary to MEN-1 may also be associated with EAS.
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Electrolyte derangement, in particular hypokalaemia and hypercalcaemia, can precipitate mild nephrogenic diabetes insipidus.
The Faculty of Medicine, Technion, Haifa, Israel
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The Faculty of Medicine, Technion, Haifa, Israel
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Severe hypocalcaemia in breast cancer with bone metastasis is a rare finding usually associated with an advanced stage of the disease. We report a case of a 45-year-old woman with a history of local ductal carcinoma in situ (DCIS) of the breast, who presented with muscle tremors and general weakness. Hypocalcaemia was evident, with a positive Chvostek sign and a serum calcium level of 5.9 mg/dL (1.47 mmol/L), phosphorus 5.9 mg/dL (normal range: 2.3–4.7 mg/dL) with normal levels of albumin, magnesium and parathyroid hormone. High oral doses of alpha calcitriol and calcium with i.v. infusion of high calcium doses were instituted, altogether sufficient to maintain only mild hypocalcaemia. A whole-body CT revealed bone lesions along the axial skeleton. A biopsy from a bone lesion revealed a metastasis of breast carcinoma. With this pathological finding, leuprolide (GNRH analogue) and chlorambucil (alkylating agent) were initiated, followed by prompt tapering of infused calcium down to full discontinuation. Serum calcium was kept stable close to the low normal range by high doses of oral alpha calcitriol and calcium. This course raises suspicion that breast metastases to the skeleton caused tumour-induced hypocalcaemia by a unique mechanism. We assume that hypocalcaemia in this case was promoted by a combination of hypoparathyroidism and bone metastasis.
Learning points
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Severe hypocalcaemia can a presenting symptom for breast cancer relapse.
Faculty of Medicine, University of Montenegro, Podgorica, Montenegro
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Faculty of Medicine, University of Montenegro, Podgorica, Montenegro
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Summary
We present a 54-year-old patient admitted to the emergency department due to loss of consciousness. The initial ECG registered monomorphic ventricular extrasystoles and prolonged QT interval (QT corrected (QTc) >500 ms). Sustained ventricular tachycardia (VT) was registered on 24-h Holter ECG monitoring, which clinically was presented as a crisis of consciousness. Coronary angiography and other visualization methods were normal. Implantable cardioverter-defibrillator (ICD) implantation was planned for the purpose of secondary prevention of sudden cardiac death (SCD). Laboratory and hormonal analyzes revealed primary hyperparathyroidism (PHPT), chronic kidney disease, and hypokalemia. Neck ultrasound showed a 25 mm, sharply outlined homogenous tumor mass which was separated from thyroid gland (TG) and exerted a mild impression on lower parts of the left lobe. Dual wash technetium-99m sestamibi parathyroid scintigraphy with single-photon emission CT (SPECT)/CT also showed the uptake of tracer behind the lower half of the left lobe of the TG. Surgical treatment, lower left parathyroidectomy, was performed, and pathohistological analysis verified parathyroid adenoma. The patient was rhythmically and hemodynamically stable for 7 days after surgery, without additional complaints, and was discharged from the hospital. Timely diagnosis of PHPT, correct assessment and surgical treatment, did not lead our patient to unnecessary ICD implantation. Our case suggests an additional intertwining of electrolyte disorders and ventricular arrhythmias in PHPT and more importantly emphasizes the need for caution when indicating ICD, even in patients with the most serious life-threatening arrhythmias.
Learning points
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Electrolyte abnormalities in PHPT can have highly malignant consequences, and the occurrence of hypokalemia in the presence of hypercalcemia is underestimated in PHPT, and the consequences can be life-threatening.
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Although hypercalcemia causes shortened QT interval, concomitant severe hypokalemia may overcome hypercalcemia and prolong QT interval, even in the absence of structural heart disease or LQTS.
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Timely diagnosis of PHPT, correct assessment and surgical treatment, do not lead to unnecessary ICD implantation.
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Summary
Primary hyperparathyroidism (PHPT) is a disease caused by overactive parathyroid glands with consequent hypercalcaemia. The main cause in 85–90% of the cases is the presence of a solitary parathyroid adenoma. The most common presentation is with asymptomatic hypercalcaemia diagnosed on routine biochemical testing. Although low serum phosphate levels are an associated finding in primary hyperparathyroidism, the diagnostic criteria for PHPT remain to be hypercalcaemia, high or inappropriately normal PTH and hypercalciuria. This case report presents a patient who presented with low phosphate levels without any other biochemical evidence of PHPT, who returned several years later with overt primary hyperparathyroidism. This report intends to raise interest among the medical fraternity whether there is a need to consider hypophosphataemia as an early sign of PHPT.
Learning points
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Primary hyperparathyroidism is a relatively common condition with varying clinical and biochemical presentation.
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The most common presentations still remain as an asymptomatic biochemical abnormality closely related to calcium, PTH and bone metabolism.
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Not much attention is usually given to associated biochemical abnormalities, and hence they are usually less investigated.
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Further research is needed to establish if patients need long-term monitoring when no obvious cause for isolated hypophosphataemia has been found.
