Summary

We report the case of an 88-year-old man hospitalized for COVID-19 with persistently very high procalcitonin (proCt) levels despite infection resolution. Since proCt is an adjunct tumor marker in the diagnosis of medullary thyroid carcinoma (MTC), serum calcitonin (Ct) was also measured showing very high levels. Computed tomography (CT) scan showed the presence of a thyroid mass and neck ultrasound revealed a solid isoechoic, inhomogeneous, 50 mm nodule in the right thyroid lobe, extended into the mediastinum. Fine needle aspiration (FNA) of the thyroid nodule confirmed the diagnosis of MTC. An ¹⁸F-fluorodopa positron emission tomography/computed tomography (PET/CT) scan revealed the presence of distant metastases in ribs, vertebrae, in the right iliac wing and the liver. Since surgery was not feasible, the patient was started on cabozantinib 40 mg/dL. After 16 months the patient is still on cabozantinib at the same dose, he reports complete autonomy in daily life activities, and serum Ct is still elevated; however, the imaging evaluation does not show signs of disease progression.

Learning points

• High procalcitonin serum values despite the absence of infection are suggestive of MTC.

• Advanced MTC with multiple metastases can have an indolent course and can go unrecognized for years.

• Cabozantinib is a valuable option for the treatment of advanced MTC.

Summary

Brain metastases as the first clinical presentation of a papillary thyroid carcinoma (PTC) are exceptional, while cavernous angiomas are common cerebral malformations. We report the case of a 36-year-old male with an incidental brain lesion mimicking a cavernous angioma on MRI. Gamma knife radiosurgery was performed, but after 6 months, the patient developed neurological symptoms, and a repeat brain MRI revealed a significant increase in the mass. The patient underwent neurosurgery, and the histological examination of the lesion revealed metastatic carcinoma of thyroid origin. PET–CT and neck ultrasound, subsequently performed, were concordant for the presence of a right lobe nodule and ipsilateral lymph nodes, both with ultrasound features suspicious of malignancy. Total thyroidectomy with central and right lateral neck dissection was performed, and histology confirmed an intrathyroidal multifocal PTC with lymph node metastases. Postoperative radioiodine was administered, and focal uptake within the thyroid bed, without distant metastases or brain remnants, was found on the post-therapeutic whole-body scan. At 2 years from diagnosis, the patient is in good health and undergoes clinical and imaging follow-up.

Learning points

• Brain cavernous angiomas are common cerebral vascular malformations that are usually diagnosed by MRI.

• Despite the high accuracy of MRI, the exam is not pathognomonic, and misdiagnosis cannot be excluded.

• Brain metastases from PTC are very rare; however, they can mimic a cavernous angioma. Therefore, the differential diagnosis should always be considered.

Summary

Familial renal glucosuria (FRG) is a rare renal tubular disorder characterized by increased urinary glucose excretion despite normoglycemia. It is most commonly caused by pathogenic variants in the solute carrier family V member 2 (SLC5A2) gene. This gene encodes the sodium–glucose cotransporter 2, crucial for glucose reabsorption. We report the case of a 44-year-old male referred to the endocrinology outpatient clinic for unexplained glucosuria despite well-controlled diabetes mellitus with metformin and gliclazide therapy. His main complaints were nocturia and an unintentional 5 kg weight loss in 1 year. A 24-h urinary collection revealed overt glucosuria (23.3 g/1.73 m²/24 h), generalized aminoaciduria, and increased uric acid excretion (fractional excretion: 6.4%). Whole-exome sequencing revealed a novel heterozygous c.469-1G>A likely pathogenic variant in the SLC5A2 gene. Specific analysis of the maturity-onset diabetes of the young type (MODY) gene panel showed no pathogenic variants in the hepatocyte nuclear factor-1A (HNF-1A; MODY3) nor in other MODY-associated genes. We assume that the association of glucosuria, aminoaciduria, and increased uric acid excretion can be explained by the combination of diabetes and the likely pathogenic SLC5A2 variant in this patient. In conclusion, we describe a well-controlled diabetic patient with FRG, associated with a novel heterozygous c.469-1G>A likely pathogenic variant in the SLC5A2 gene.

Learning points

• The diagnosis of a renal tubular disorder should be considered in patients with unexplained glucosuria and diabetes mellitus, especially if the latter is well controlled.

• FRG usually presents with glucosuria but may be associated with generalized aminoaciduria and hyperuricosuria.

• Genetic analysis should be considered in patients with young-onset diabetes and glucosuria, particularly with a positive family history.

Summary

Bariatric surgery is increasingly being accepted as a viable treatment for managing the growing obesity epidemic. Roux-en-Y gastric bypass (RYGB) is one of the most commonly performed procedures. Perforated duodenal ulcer following RYGB is a rare condition with a low incidence. We report a case of a patient with a perforated duodenal ulcer post RYGB, and the surgical approach. A 66-year-old man with hypertension and a history of laparoscopic RYGB for class III obesity was admitted to the emergency department with severe epigastric pain radiating to the right side of his abdomen and right shoulder, associated with nausea and vomiting. Computed tomography (CT) showed intraperitoneal free fluid, a thickened wall of the duodenum and free air, duodenal perforation was suspected. The patient underwent exploratory laparoscopy that revealed a perforated duodenal ulcer that was closed with an absorbable barbed suture and omental patch. Perforated ulcers in excluded segments after RYGB are a rare entity with a challenging diagnosis, and clinicians should be aware of and have a low threshold for diagnostic laparoscopy.

Learning points

• Roux-en-Y gastric bypass (RYGB) is one of the most commonly performed procedures in bariatric surgery.

• Perforated ulcers in excluded segments after RYGB are a rare entity with a challenging diagnosis.

• The pathophysiology of this perforation is not clear, but several mechanisms have been proposed. Helicobacter pylori has been implicated.

• Clinicians should be aware and have a low threshold for diagnostic laparoscopy for a patient who has acute abdominal pain after RYGB, despite negative diagnostic measures.

Summary

Hypoglycemia is one of the paraneoplastic syndrome manifestations that arise from primary and secondary liver cancer. Hypoglycemia usually presents in the late stage of the disease and indicates a poor prognosis. This case series displays the characteristics profile of patients with primary and secondary liver cancer who are presented with hypoglycemia in a tertiary referral hospital in Indonesia. The study included 41 liver cancer patients who were presented with hypoglycemia. Hepatocellular carcinoma was diagnosed in 51.2% of patients, metastatic liver disease in 14.6% of patients, and undiagnosed liver cancer in 34.1% of patients. The mean age was 47.7 years with male predominance (65.9%). Jaundice was found in 58.5% and hepatomegaly in 70.7% of patients. The mean (± S.D.) initial blood glucose was 42.15 ± 17.11 mg/dL and the Child–Pugh score was 9.93 ± 2.11. Based on imaging, tumor diameter was 12.6 ± 6.9 cm, multiple (61%), and involving both lobes (61%). Treatments for hypoglycemia included oral/enteral feeding, intravenous dextrose, and steroids. No treatment was given for the cancer because all patients were in an advanced stage. The treatment resulted in 41.5% blood glucose being controlled, 56.1% refractory, and 2.4% persistent. Mortality was 70.7% and in average occurred 5.76 ± 4.99 days after hypoglycemia. The mainstay of treatment in these cases is treating the tumor with cytoreduction. However, it was difficult to do cytoreduction because the tumor was already in an advanced stage. Beneficial supportive treatments for maintaining normal blood glucose are frequent meals, dextrose infusion, steroids, and glucagon.

Learning points

• Hypoglycemia in liver cancer occurs due to the failure of the liver to fulfill body glucose demand because the liver parenchyma has been largely replaced by the tumor, in addition to the high production of insulin growth factor (IGF).

• Hypoglycemia is often caused by islet cell and non-islet cell tumors, with a higher occurrence in non-islet cell tumors due to paraneoplastic syndrome and the high metabolic requirements of the tumor.

• The mainstay of NICTH treatment is treating the tumor with cytoreduction. However, in an advanced stage, cytoreduction therapy is often challenging to conduct. Beneficial supportive treatments for controlling blood glucose are frequent meals, dextrose infusion, and the injection of steroids and glucagon.

• Steroids play a beneficial role in the treatment of persistent hypoglycemia in hepatocellular carcinoma by stimulating gluconeogenesis and increasing lipolysis. Steroids also have roles in the inhibition of peripheral glucose intake, suppression of big IGF-2 production, and modulation of the GH–IGF axis.

Summary

Thyroid storm is a clinical diagnosis characterized by life-threatening multisystemic organ involvement in the setting of uncontrolled hyperthyroidism. Current estimates suggest a mortality rate of up to 30%. Treatment often consists of the administration of thionamide medications, iodine solution(s), corticosteroids, and beta-blockers; in extreme circumstances, both plasmapheresis and thyroidectomy are subsequent therapeutic options. Thionamides are typically administered orally, with the intent of preventing further thyroid hormone synthesis; however, in the literature, there are instances whereby oral access cannot be obtained, and alternative routes of administration are required. We present a case of a patient who presented with a thyroid storm due to lack of adherence to methimazole. During admission, he was found to have significant abdominal pain and ultimately a duodenal perforation requiring strict nil-per-os (NPO) status, due to which he was unable to receive oral thionamides. Due to the lack of availability of intravenous formulations of thionamides in the United States, this patient was treated with an enema compound of propylthiouracil for a total of five per rectum (PR) doses. He would later develop hepatocellular injury, requiring discontinuation and eventual transition to oral methimazole. The literature pertaining to alternative-route thionamide administration is scant, and therefore this case report and literature review is written to provide an up-to-date review and further educate all levels of clinicians about this infrequent (but emergent) situation.

Learning points

• Thyroid storm is a clinical diagnosis for which urgent recognition is required to prevent untoward mortality.

• Treatment for thyroid storm requires prompt administration of thionamides, iodine, corticosteroids, and beta-blockers. In extreme circumstances, treatment considerations include plasmapheresis and thyroidectomy.

• Infrequently, patients with a thyroid storm may not be able to tolerate oral medications, for which alternative routes of access are required.

• Currently, available alternatives include intravenous methimazole (in Europe and Japan), as well as both enema and suppository preparations of propylthiouracil and methimazole.

Summary

At the end of the 19th century, an 18-year-old lady gave birth to a well-proportioned, though very small, son. After delivery, the mother developed a full-grown beard, whereas the son always remained of small stature. The mother developed diabetes mellitus and died, aged 59, from a complicated severe cold. The son died at the age of 91 because of chronic kidney disease. The differential diagnosis in the son is isolated growth hormone deficiency. The mother might have suffered luteoma of pregnancy, polycystic ovary syndrome (PCOS), or Sertoli–Leydig cell tumor(s). The two cases are apparently coincidental/not related in pathophysiology.

Learning points

• Hirsutism occurring directly postpartum can have several causes.

• Patients with isolated growth hormone deficiency can live a long life without the substitution of growth hormone.

• Coincidence does not necessarily imply correlation.

• In the past, patients with endocrine disorders like severe hirsutism or small stature were employed at circuses and fairs to entertain the audience as curiosities.

Summary

The resistance to thyroid hormone syndrome (RTHβ) occurs uncommonly and requires a high level of clinical suspicion and specific investigations to reach a precise diagnosis and to avoid unnecessary and potentially harmful therapies. We report a case of a young male patient referred to our unit for SARS-CoV-2 infection and atrial fibrillation with elevated thyroid hormones and non-suppressed thyroid-stimulating hormone (TSH), for which antithyroid therapy was prescribed. A mood disorder was reported in the medical history. The family history was unknown as the patient was adopted. Thyroid-specific antibodies were undetectable, and thyroid ultrasound revealed a normal thyroid gland without nodules. After the resolution of SARS-CoV-2 infection, the diagnostic workup continued, and the pituitary MRI revealed a small area ascribable to a microadenoma. Due to atrial fibrillation, the execution of the T3 test was contraindicated. The octreotide long-acting release (LAR) test showed an initial reduction of free thyroid hormones levels at first administration, which was consistent with the presence of a TSH-secreting pituitary tumour, although an escape from the response was observed after the following two injections of octreotide LAR. Indeed, the genetic investigation revealed a variant in heterozygosity of the THRβ gene (Pro453Ser), thus leading to an RTHβ diagnosis, and, therefore, medical treatment with triiodothyroacetic acid was initiated. After 2 years from the SARS-CoV-2 infection, the patient continues the follow-up at our outpatient clinic, and no other medical interventions are needed.

Learning points

• RTHβ is a rare genetic syndrome characterised by discrepant thyroid function tests and by a dissociation between the observed hormone levels and the expected patient signs and symptoms.

• Features of thyroid hormone deficiency in TR-ß dependent tissues (pituitary gland, hypothalamus, liver and neurosensitive epithelia), as well as thyroid hormone excess in TR-α-dependent tissues (heart, bone, skeletal muscle and brain), may coexist in the same individual.

• Clinical pictures can be different even when the same variant occurs, suggesting that other genetic and/or epigenetic factors may play a role in determining the patient’s phenotype.

• Differentiating RTHβ from a TSH-secreting pituitary tumour is very difficult, especially when a concomitant pituitary adenoma is detected during diagnostic workup. The injection of long-acting somatostatin analogues can help differentiate the two conditions, but it is important to detect any interference in the dosage of thyroid hormones to avoid an incorrect diagnosis.

• Genetic testing is fundamental to prevent unnecessary and potentially harmful therapies.

• Medical treatment with triiodothyroacetic acid was demonstrated to be effective in reducing thyroid hormone excess and controlling symptoms.

Summary

X-linked hypophosphatemic rickets (XLH), the most prevalent form of inherited hypophosphatemic rickets, is caused by loss-of-function mutations in the gene encoding phosphate-regulating endopeptidase homolog, X-linked (PHEX). This case series presents 14 cases of XLH from Gulf Cooperation Council (GCC) countries. The patients’ medical history, biochemical and radiological investigative findings, as well as treatment responses and side effects from both conventional and burosumab therapy, are described. Cases were aged 2–40 years at diagnosis. There were two male cases and 12 female cases. All cases were treated with conventional therapy which resulted in a lack of improvement in or worsening of the clinical signs and symptoms of rickets or biochemical parameters. Side effects of conventional therapy included nausea, diarrhea, abdominal pain, nephrocalcinosis, and hyperparathyroidism, which affected the patients’ quality of life and adherence to treatment. In the 10 patients treated with burosumab, there was a marked improvement in the biochemical markers of rickets, with a mean increase in serum phosphate of +0.56 mmol/L and tubular maximum phosphate reabsorption (TmP) to glomerular filtration rate (GFR) ratio (TmP/GFR) of +0.39 mmol/L at 12 months compared to baseline. Furthermore, a mean decrease in serum alkaline phosphatase (ALP) of −80.80 IU/L and parathyroid hormone (PTH) of −63.61 pmol/L at 12 months compared to baseline was observed in these patients. Additionally, patients treated with burosumab reported reduced pain, muscle weakness, and fatigue as well as the ability to lead more physically active lives with no significant side effects of treatment.

Learning points

• Conventional therapy resulted in a suboptimal response, with a lack of improvement of clinical signs and symptoms.

• Side effects of conventional therapy included nausea, diarrhea, abdominal pain, nephrocalcinosis, and hyperparathyroidism, which affected the patients’ quality of life and adherence to treatment.

• Burosumab demonstrated marked improvements in the biochemical markers of rickets, in addition to reducing pain, muscle weakness, and fatigue.

• There were no significant side effects associated with burosumab therapy.

Summary

Iodine nutrition is a growing issue within the USA due to newer trends of non-iodized salts. There are no recent reviews looking at the current state of iodine deficiency-induced hypothyroidism in children in the USA. We performed a retrospective chart review at our tertiary pediatric endocrine clinic; four met the diagnostic criteria for iodine deficiency defined by a low urine iodine level. We further characterized severity of disease, risk factors, goiter, thyroid labs and antibodies. All cases had significant goiter and were diagnosed within the last 2 years. One case had iodine deficiency due to no iodized salt intake along with concurrent diagnosis of developmental delay and multiple food allergies, while others involved the use of non-iodized salts. Two cases had iodine deficiency along with autoimmunity. It is critical to obtain a dietary history for all patients who present with goiter and/or hypothyroidism. There may be a need to consider reevaluating current preventative measures for iodine deficiency, especially for certain vulnerable populations such as children who do not consume iodized salt.

Learning points

• In recent decades, iodine nutrition has become a growing concern due to changing dietary patterns and food manufacturing practices.

• A dietary history is crucial to obtain in children presenting with hypothyroidism and goiter, especially in children with restrictive diets due to behavioral concerns, developmental delays, or multiple food allergies.

• Of the 12 different types of salts commercially available, only table salt contains iodine in an appropriate amount; thus, individuals using specialty salts can develop mild to moderate iodine deficiency-related thyroid disease.