Calcaneus metastasis: a rare presentation of poorly differentiated thyroid cancer.

Summary: A 60-year-old woman presented to our clinic with an acute onset 3 months history of right ankle pain. The patient had a history of poorly differentiated thyroid cancer, which was treated with total thyroidectomy, left lateral neck dissection levels II-V and central neck dissection levels VI-VII followed by postoperative I-131 radioactive iodine (131I) ablation therapy 3.7 GBq 6 months ago. The post-131I WBS showed residual iodine-avid thyroid tissue with no other iodine-avid disease or metastasis. SPECT/CT of the neck and chest showed nonavid bilateral pulmonary nodules, discrete nodal masses in mediastinum and nonavid bone lesions. FDG-PET CT scan showed FDG-avid mediastinal lymph nodes (LN), innumerable non-FDG-avid subcentimetric pulmonary nodules and few FDG-avid lytic lesions in the skeleton. X-ray and MRI of the right ankle showed a well-marginated lytic lesion in the posterior body of calcaneus and 5 × 6 cm soft tissue mass lesion, respectively. The histopathology of the calcaneus mass confirmed a positive immunostaining for thyroid origin which includes thyroglobulin and TTF-1 with PAX-8. Endobronchial mediastinal and bronchial LN biopsy confirmed thyroid cancer metastasis. Gene mutation showed HRAS and GNA13 with a high tumor mutational burden. We describe a rare case of poorly differentiated thyroid cancer in a patient who presented with right ankle pain; we confirmed the cause to be a calcaneus metastasis from the thyroid cancer, with calcaneus being an extremely rare site for bone metastases. Gene mutations points toward treatment with immune checkpoint inhibitors. Learning points: Poorly differentiated thyroid carcinoma (PDTC) usually metastasizes to lung and bone but can rarely occur in the calcaneus. Patients with distant metastases have significantly worse long-term prognosis. Radiotherapy is effective in reducing the metastatic pains as well as reducing the size of the metastasis. PAX-8 staining can be used to differentiate thyroid carcinomas from lung adenocarcinomas. The importance of searching for gene mutations to decide the treatment of PDTC.

Hypertensive Crisis in a Patient With a Functioning Mesenteric Paraganglioma: Dramatic Response to Octreotide Treatment.

Background/Objective: To report a dramatic and immediate clinical and biochemical response during treatment with octreotide in a patient with a functioning mesenteric paraganglioma (PGL). Case Report: A 44-year-old woman was admitted with a severe hypertensive crisis and a blood pressure reaching 260/150 mm Hg. She was 2 months postpartum and had been previously diagnosed with pre-eclampsia. Secondary hypertension was suspected. This was confirmed by finding a 6 × 5-cm2 retroperitoneal mass located using 68-Gallium DOTA-octreotate positron emission tomography/computed tomography and a grossly elevated plasma catecholamine level of 93 000 pmol/L (normal reference range: 650-2433 pmol/L). Treatment was immediately started with high doses of long- and short-acting octreotide. After 6 weeks and before surgery, the patient was normotensive, with a blood pressure of 120/70 mm Hg and a norepinephrine level of 6000 pmol/L. The tumor resection was uneventful, and histology confirmed the diagnosis. Following the surgery, the patient remained normotensive without any medications. Discussion: PGLs and pheochromocytomas are neuroendocrine tumors, and most have receptors for octreotide. This case and another patient previously reported responded dramatically to treatment with a high dose of octreotide. Earlier reports of patients failing to respond are likely to have been the result of using a smaller octreotide dose. Conclusion: We conclude that high doses of short- and long-acting octreotide are valuable in severely hypertensive patients. Our experience suggests that octreotide is of value in other patients with PGLs and pheochromocytomas. The response is rapid, sustained, effective, and with minimal reported side effects. To the best of our knowledge, this is the first report of a hypertensive crisis in a functional mesenteric PGL.

Evolution of Minimally Invasive Adrenal Surgery at a Tertiary Care Centre in Oman.

Objectives: This study aimed to review the case records and report the outcomes of open and laparoscopic adrenalectomy (LA) cases. Methods: This retrospective study included patients who underwent adrenal surgery from January 2010 to December 2020 at Sultan Qaboos University, Muscat, Oman. Demographic details, indications, surgical approaches, intra-operative data, complications, final pathology and outcome at the last follow-up were analysed. Results: A total of 52 patients underwent 61 adrenalectomies; six patients had a bilateral procedure while three patients had to undergo revision surgery resulting in a total of 55 individual procedures. Open adrenalectomy (OA) was performed on 11 patients and 44 patients underwent LA. Most patients (n = 27) were obese with a body mass index >30. Functional adenoma was excised in 36 patients with final diagnosis of Conn's syndrome in 15, pheochromocytoma in 13 and Cushing's syndrome in nine patients. Five patients had surgery for oncological indications. Non-functional adenoma was excised in 13 patients, with a mean size of 8.9 cm (range: 4-15 cm). The mean duration of surgery was less in laparoscopic procedure compared to open (199 versus 246 minutes). The mean estimated blood loss in LA was significantly less (108 versus 450 mL; P <0.05). Out of 55 procedures, only one patient developed Clavien-Dindo grade 2 complication. Conclusion: Both LA and OA were safely performed at the researchers' institution. There is a growing trend for LA, and with experience, the duration of surgery and estimated mean blood loss are demonstrating a positive trend.

Papillary follicular variant thyroid cancer in a malignant struma ovarii: a report of a rare case.

Summary: A 33-year-old female presented in 2013 with left flank pain. Ultrasound and MRI pelvis showed a complex mass 9 × 7 cm arising from the left ovary suggestive of ovarian torsion. She underwent a laparoscopic cystectomy, but the patient was lost to follow-up. Three years later, she presented with abdominal distension. Ultrasound and CT scan revealed a solid left ovarian mass with ascites and multiple peritoneal metastasis. Investigations showed elevated CA 125, CA 19-9. Ovarian malignancy was suspected. She underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy on November 2016. The histopathology confirmed a well-differentiated thyroid cancer of ovarian origin with features of a papillary follicular variant without evidence of ovarian cancer and the thyroglobulin (Tg) level was elevated, more than 400 consistent with the diagnosis of malignant struma ovarii. The follow-up post-surgery showed normalization of CA 125, CA 19-9 and Tg. The patient underwent total thyroidectomy on January 2017. The histology was benign excluding thyroid cancer metastases to the ovary. She was started on thyroxine suppression, following which she received two ablation doses 131iodine (131I) each 5.3 GBq. The Tg remains slightly elevated at less than 10. 131I WBS showed no residual neck uptake and no distant avid metastasis. She was planned for molecular analysis which may indicate disease severity. We describe a case of malignant struma ovarii with widespread metastatic dissemination and a good response to surgery and 131I treatment without recurrence after 5 years of follow-up. The Tg remains slightly elevated indicating minimal stable residual disease. Learning points: Malignant struma ovarii is a rare disease; diagnosis is difficult and management is not well defined. Presentation may mimic advanced carcinoma of the ovary. Predominant sites of metastasis are adjacent pelvic structures. Thyroidectomy and 131iodine therapy should be considered. The management should be similar to that of metastatic thyroid cancer.

Euthyroid athyroxinemia - a novel endocrine syndrome.

A 55-year-old female was referred with abnormal thyroid function tests (TFTs); the free thyroxine level (FT4) was undetectable <3.3 pmol/L (normal: 7.9-14.4), while her FT3, TSH and urinary iodine levels were normal. She was clinically euthyroid with a large soft lobulated goitre that had been present for more than thirty years. She received an injection of recombinant human TSH (rhTSH) following which there was a progressive rise of the FT3 and TSH levels to 23 pmol/L and >100 mIU/L respectively at 24 h, The FT4 however remained undetectable throughout. Being on thyroxine 100 µg/day for one month, her FT4 level increased to 15 pmol/L and TSH fell to 0.08 mIU/L. Four years earlier at another hospital, her FT4 level had been low (6.8 pmol/L) with a normal TSH and a raised Tc-99 uptake of 20% (normal<4%). We checked the TFTs and Tc-99 scans in 3 of her children; one was completely normal and 2 had euthyroid with soft lobulated goitres. Their Tc-99 scan uptakes were raised at 17% and 15%, with normal TFTs apart from a low FT4 7.2 pmol/L in the son with the largest thyroid nodule. This is a previously unreported form of dyshormonogenesis in which, with time, patients gradually lose their ability to synthesize thyroxine (T4) but not triiodothyroxine (T3). LEARNING POINTS: This is a previously unreported form of dyshormonogenetic goitre.This goitre progressively loses its ability to synthesize T4 but not T3.The inability to synthesize T4 was demonstrated by giving rhTSH.

Paget's Disease in an Omani: Long-term Improvement Following a Single Injection of Zoledronic Acid.

Paget's disease of bone is a patchy skeletal disorder characterized by an increase in bone resorption and formation in the affected areas. It affects up to 3% of individuals of Anglo-Saxon origin over the age of 40 years but is rare in Arabs. Although most patients are asymptomatic, a variety of symptoms and complications may develop directly from bone involvement or secondarily to compression by bone expansion and increased blood flow. The disease can be treated by using medications that inhibit bone resorption, such as calcitonin and the bisphosphonates. Here we describe the case of an Omani patient with the disease, involving the skull, spine, pelvis, and tibia. He presented to the endocrine clinic in Sultan Qaboos University Hospital with a six-year history of headache, bone pain, progressive skull enlargement, and left-sided deafness. His alkaline phosphatase (ALP) level was 1500 U/L. His disease responded gradually to six months of subcutaneous and nasal calcitonin followed by a single 5 mg intravenous injection of zoledronic acid. This resulted in a further progressive reduction of his bone pain, skull size, and improvement in his hearing, as well as normalization of his serum ALP levels after one-year. This effect has been sustained for 3 years.

Catecholamine-secreting carotid body paraganglioma: successful preoperative control of hypertension and clinical symptoms using high-dose long-acting octreotide.

UNLABELLED: A 48-year-old hypertensive and diabetic patient presented with a 10-year history of progressive right facial pain, tinnitus, hearing loss, sweating, and palpitations. Investigations revealed a 5.6 cm vascular tumor at the carotid bifurcation. Her blood pressure (BP) was 170/110, on lisinopril 20 mg od and amlodipine 10 mg od and 100 U of insulin daily. A catecholamine-secreting carotid body paraganglioma (CSCBP) was suspected; the diagnosis was confirmed biochemically by determining plasma norepinephrine (NE) level, 89 000 pmol/l, and chromogranin A (CgA) level, 279 µg/l. Meta-iodobenzylguanidine and octreotide scanning confirmed a single tumor in the neck. A week after giving the patient a trial of octreotide 100 µg 8 h, the NE level dropped progressively from 50 000 to 25 000 pmol/l and CgA from 279 to 25 µg/l. Treatment was therefore continued with labetalol 200 mg twice daily (bid) and long-acting octreotide-LA initially using 40 mg/month and later increasing to 80 mg/month. On this dose and with a reduced labetalol intake of 100 mg bid, BP was maintained at 130/70 and her symptoms resolved completely. CgA levels returned to normal in the first week and these were maintained throughout the 3 month treatment period. During tumor resection, there were minimal BP fluctuations during the 10 h procedure. We conclude that short-term high-dose octreotide-LA might prove valuable in the preoperative management of catecholamine-secreting tumors. To the best of our knowledge, this is the first report on the successful use of octreotide in a CSCBP. LEARNING POINTS: The value of octreotide scanning in the localization of extra-adrenal pheochromocytoma.Control of catecholamine secretion using high-dose octreotide.This is a report of a rare cause of secondary diabetes and hypertension.

Cushing's Disease: Sustained remission in five cases induced by medical therapy with the dopamine agonist cabergoline.

We report five cases of Cushing's disease where the patients were given a therapeutic trial of cabergoline. Morning serum cortisol, adrenocorticotrophic hormone (ACTH), and sleeping cortisol concentrations were significantly raised. Magnetic resonance imaging (MRI) scans revealed pituitary microadenomas in 3 patients but were normal in the others. Ectopic ACTH production was excluded in the 2 patients with normal MRI scans. All were given a therapeutic trial of cabergoline (1 mg daily). Four patients responded with a prompt fall in serum cortisol levels and had a sustained clinical and biochemical remission for 378, 44, 28 and 14 days, respectively. One patient failed to respond. In conclusion, we suggest that all patients with Cushing's disease should undergo a therapeutic trial of cabergoline. Responders can then be prepared for surgery or, if needed, treated medically in the long term.

Vitamin D Status in Pregnant Omanis: A disturbingly high proportion of patients with low vitamin D stores.

OBJECTIVES: The objective of this study was to determine the vitamin D status of pregnant Omanis by measurement of their circulating 25 hydroxy vitamin D levels. METHODS: Blood samples were obtained from a cohort of 103 consecutive healthy pregnant Omanis at the Armed Forces Hospital, Muscat, on their first antenatal visit. The study took place in May, June and July 2010. RESULTS: Vitamin D deficiency was present in 34 (33%) of patients (25OHD3 <25 nmol/L), 'at risk' levels were found in 67 (65%) patients (25OHD3 25-50 nmol/L); two patients (1.9%) had values between 50 and 75 nmol/L, and no patients in the optimal range >75 nmol/L. CONCLUSION: If confirmed, these findings indicate the need for vitamin D replacement during pregnancy and lactation. Although not evidence based we recommend at least 1000 IU of cholecalciferol, (vitamin D3) daily.

VIPoma Crisis: Immediate and life saving reduction of massive stool volumes on starting treatment with octreotide.

We report the case of a 57-year-old male physician who presented with a life threatening secretory and refractory diarrhoea of around 20 L/day. This was complicated by severe hypotension, hypokalaemia, hypercalcaemia, renal failure requiring dialysis, metabolic acidosis, cardiorespiratory arrest and ventilation for 12 days. His diarrhoea responded immediately to the first dose of a therapeutic trial of subcutaneous octreotide 100 mcg 8 hourly which was started on clinical grounds alone before any investigations were carried out. After one day he was extubated and his blood pressure returned to normal. When a functioning neuroendocrine tumour is suspected clinically, the use of octreotide can, as in this case, be life saving.

Clinically-Defined Maturity Onset Diabetes of the Young in Omanis: Absence of the common Caucasian gene mutations.

OBJECTIVES: We are seeing a progressive increase in the number of young patients with clinically defined maturity onset diabetes of the young (MODY) having a family history suggestive of a monogenic cause of their disease and no evidence of autoimmune type 1 diabetes mellitus (T1DM). The aim of this study was to determine whether or not mutations in the 3 commonest forms of MODY, hepatic nuclear factor 4α (HNF4α), HNF1α and glucokinase (GK), are a cause of diabetes in young Omanis. METHODS: The study was performed at Sultan Qaboos University Hospital (SQUH), Oman. Twenty young diabetics with a family history suggestive of monogenic inheritance were identified in less than 18 months; the median age of onset of diabetes was 25 years and the median body mass index (BMI) 29 at presentation. Screening for the presence of autoimmune antibodies against pancreatic beta cells islet cell antibody (ICA) and glutamic acid decarboxylase (GAD) was negative. Fourteen of them consented to genetic screening and their blood was sent to Prof. A. Hattersley's Unit at the Peninsular Medical School, Exeter, UK. There, their DNA was screened for known mutations by sequencing exon 1-10 of the GCK and exon 2-10 of the HNF1α and HNF4α genes, the three commonest forms of MODY in Europe. RESULTS: Surprisingly, none of the patients had any of the tested MODY mutations. CONCLUSION: In this small sample of patients with clinically defined MODY, mutations of the three most commonly affected genes occurring in Caucasians were not observed. Either these patients have novel MODY mutations or have inherited a high proportion of the type 2 diabetes mellitus (T2DM) susceptibility genes compounded by excessive insulin resistance due to obesity.

Multiple Bone Metastases in a Patient with Differentiated Thyroid Cancer (DTC): Complete resolution following thyroidectomy and four ablation doses of I-131.

Multiple bone metastases from a differentiated thyroid cancer are usually incurable. We report the case of a young Omani woman who presented with 8 discrete skeletal lesions three years after a total thyroidectomy. Following four ablation doses of I-131 she has remained in clinical and biochemical remission for over five years. An extraordinary aspect of this case was the persistent refusal of her husband to use contraception either for himself or his wife. This resulted in her treatment being delayed for more than 6 years during which time the patient delivered and breastfed four additional healthy babies.

The Diagnosis and Management of Severe Hypercalcaemia: A simplified approach - Report of five cases.

Hypercalcaemia is a common medical problem, can be a manifestation of many diseases and, when severe, can represent a life-threatening medical emergency. Making the correct diagnosis is important to prevent unnecessary investigations and parathyroidectomies. At Sultan Qaboos University Hospital, Oman, we have recently seen five patients with severe hypercalcaemia (calcium ≥3.5 mmol/L), most of whom had been misdiagnosed for months or even years. The clinical examination, evaluation of the fasting serum calcium, phosphate, creatinine and 24-hour urine calcium levels together with a review of their radiographs accurately predicted the pathophysiology of the disorder and successfully guided our investigative procedures well before the results of hormone assays became available.

Familial mineralocorticoid induced hypertension in the sultanate of oman.

OBJECTIVES: In Oman, many hypertensive patients with a family history of the disease respond to treatment with spironolactone, a mineralocorticoid receptor (MC-R) blocking agent thus suggesting a high prevalence of mineralocorticoid (MC) induced disease. The aim of this study was to document the prevalence of MC induced disease in patients with a positive family history of hypertension (HTN). METHODS: Serum calcium, potassium, creatinine, aldosterone and renin levels were measured under standard conditions in all patients together with an abdominal ultrasound scan and an adrenal computed tomography (CT) scan in four patients. RESULTS: In this small study, we show that 18 of the 27 patients (66%) had undetectable (suppressed) renin levels with usually normal aldosterone values (14 patients) and respond to treatment with spironoactone. CONCLUSION: We suggest that MC induced hypertension is likely to be common in the Middle East. In evolutionary terms, this makes sense as the ability to conserve salt in hot climates might be expected to confer a definite survival advantage.