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

An 89-year-old woman presented with a 6-year history of occasional episodes of impaired consciousness that were relieved by ingestion of a snack. Three months before presenting to our hospital, she had been hospitalized in a local hospital with subdural hematoma caused by a head contusion, where previously unrecognized hypoglycemia was discovered. Fasting plasma glucose concentration was 37 mg/dL, with a relatively high serum level of insulin (34.9 µU/mL). Computed tomography showed a 14 mm hyperenhancing tumor in the tail of the pancreas and she was referred to our hospital for further investigation. A prolonged fasting test revealed the plasma glucose concentration reduced to 43 mg/dL (2.4 mmol/L) at 8 h after the last meal. Serum insulin, proinsulin, and C-peptide concentrations were 21.1 µU/mL, 16.9 pmol/L, and 2.72 ng/mL, respectively. Subsequent intravenous administration of 1 mg of glucagon increased the plasma glucose concentration to 76 mg/dL (4.2 mmol/L). Moreover, the insulin-to-C-peptide molar ratio was 0.14. These data indicated the presence of insulinoma. Interestingly, serum anti-insulin antibodies were elevated (21.1 U/mL), although she had no history of taking exogenous insulin injection, alpha lipoic acid, or sulfhydryl group-containing agents. Human leukocyte antigen (HLA) typing revealed HLA-DRB1*0407 and HLA-DRB1*1405 alleles. Treatment with diazoxide prevented hypoglycemia, but was discontinued due to weight gain and leg edema. Elevated serum anti-insulin antibodies persisted almost 1 year after the diagnosis of insulinoma. We present a rare case of insulinoma concomitant with serum anti-insulin antibodies.

Learning points

• Insulinoma presenting with concomitant anti-insulin antibodies appears rare.

• Insulin/C-peptide molar ratio and serum insulin concentration are useful for differentiating insulinoma and autoimmune syndrome.

• Flash glucose monitoring systems appear suitable for evaluating treatment outcomes.

Summary

Riedel’s thyroiditis is the rarest form of thyroiditis, occasionally resulting in rapid thyroid enlargement and potential tracheal obstruction. Here, we detail the case of an 81-year-old woman with a medical history including Hodgkin lymphoma, Hashimoto’s thyroiditis, and multinodular goiter. She presented to the emergency room with stridor, cervical swelling, and breathing difficulties for over 2 days. CT scans revealed substantial thyroid enlargement causing significant glottal and tracheal compression, to a minimum tracheal diameter of 7 mm. Due to the severity of the compressive symptoms, orotracheal intubation and mechanical ventilation were deemed necessary. Surprisingly, despite the initial suspicion of malignancy given the rapid growth in the elderly, subsequent cytological and histological evaluations indicated a benign form of invasive fibrous thyroiditis – Riedel’s thyroiditis. Although surgical intervention was advised, the patient declined and opted for endobronchial treatment with a prosthetic stent and subsequent treatment with systemic glucocorticoids. Following successful treatment, she was discharged within a week and resumed normal activities without respiratory distress. This case is noteworthy for its rapid benign mass growth, rare emergent presentation, and the patient’s advanced age.

Learning points

• The rapid enlargement of the thyroid gland in elderly patients poses a diagnostic challenge, stemming from the higher occurrence of aggressive thyroid carcinomas.

• Despite the clinical presentation, a comprehensive diagnostic workup, including fine-needle aspiration and core-needle biopsy, is crucial for accurately distinguishing between benign and malignant causes of thyroid nodule enlargement.

• This case report illustrates diverse treatment options for Riedel’s thyroiditis, and the importance of individualized treatment plans based on the degree of airway obstruction, patient preferences, and response to initial interventions.

• Clinicians should contemplate the inclusion of glucocorticoids in the therapeutic regimen for Riedel’s thyroiditis, particularly in cases where surgical intervention is not feasible or declined by the patient.

Summary

Although most published cases of lead poisoning come from occupational exposures, some traditional remedies may also contain toxic amounts of lead. Here, we report the case of a 58-year-old female who presented with abdominal pain, generalized tiredness, and decreased food intake, with anemia and elevated levels of lead. The patient was found to be taking herbal capsules for diabetes prior to the presentation. This case highlights the need for increased awareness that some herbal remedies may contain potentially harmful levels of heavy metals, and people who use them are at risk of developing associated toxicities.

Learning points

• Individuals who support traditional medicine often incorrectly believe that herbal remedies for diabetes are free from side effects, leading them to favor these treatments over contemporary medications.

• Herbal medications are freely available online, even without a prescription.

• The accessibility of herbal medicines without prescriptions, coupled with the false belief in their lack of side effects, misleads educated individuals toward quackery treatments. Misinformation spread via social media exacerbates this issue.

• Heavy metals are present in toxic levels in the drugs, causing complications.

• Lead is the most common heavy metal found in such herbal medicines.

• Lead poisoning leads to anemia and other systemic complications which could have been fatal if not found in time.

Summary

Thyroid-stimulating hormone-secreting pituitary adenomas (TSHomas) are rare, accounting for less than 1% of all pituitary adenomas. We present a case of hyperthyroidism secondary to a likely TSHoma and coexisting functional thyroid adenoma. Laboratory errors and familial abnormalities in thyroid function tests were ruled out, and a diagnosis of the toxic thyroid adenoma was confirmed on a thyroid uptake scan. However, the triiodothyronine suppression test was contraindicated due to the patient’s cardiovascular disease, and the thyrotropin-releasing hormone stimulation test, measurement of glycoprotein hormone alpha-subunit, and genetic testing were unavailable. Magnetic resonance imaging of the brain revealed a suprasellar pituitary macroadenoma measuring 40 mm × 20.3 mm × 17 mm. The patient was initiated on carbimazole; however, thyroid stimulating hormone and thyroxine levels remained elevated. The patient declined trans-sphenoidal surgery and was treated with radioactive iodine to manage the toxic thyroid adenoma, leading to reduced thyroxine levels and symptom improvement. Unfortunately, the patient passed away before long-acting somatostatin analogs became available. This case highlights the diagnostic and therapeutic challenges involved in managing thyrotoxicosis with dual etiology.

Learning points

• Hyperthyroidism can have multiple etiologies, which can coexist in the same patient.

• Persistent discordant thyroid function tests warrant further investigation.

• The gold standard for diagnosis of TSHomas remains immunohistochemical analysis of the tumor tissue.

Summary

Insulin autoantibody syndrome (IAS) or Hirata’s disease is a rare condition characterized by recurrent fasting hypoglycaemic and postprandial hyperglycaemic episodes. Insulin autoantibodies are diagnostic for the condition. Hirata’s disease has been seen to be associated with other autoimmune conditions. Vitiligo is a common depigmentation disorder whose exact cause is unknown but thought to have an autoimmune aetiology. Although autoimmunity plays a role in the pathogenesis of both the diseases, association between the two has not been reported till date. In our case, a 72-year-old Indian woman with vitiligo for the past 30 years presented with recurrent episodes of fasting hypoglycaemia. She was found to have very high levels of fasting insulin, C-peptide, and insulin antibody and was diagnosed with IAS. Thus, we conclude that the clinical spectrum of Hirata’s disease has to be taken as more heterogenous than previously assumed.

Learning points

• Insulin autoantibody syndrome (IAS) or Hirata’s disease is a rare condition characterized by recurrent fasting hypoglycaemic and postprandial hyperglycaemic episodes in which insulin plays a major role.

• Insulin autoantibodies are diagnostic for IAS. The endocrine insulin and its autoantibodies play a major role in the pathogenesis of the disease.

• Vitiligo is a common depigmentation disorder whose exact cause is unknown but thought to have an autoimmune aetiology.

• IAS and vitiligo are two diseases with autoimmune aetiology which has been seen to be associated with each other (the first case to be reported).

• The clinical spectrum of Hirata’s disease has to be taken as more heterogenous than previously assumed.

• On dealing with autoimmune diseases, we should also keep in mind about other diseases with autoimmune pathogenesis.

Summary

We report the case of a male patient with papillary thyroid cancer, familial thoracic aortic aneurysm and dissection, and a variation in the MYH11 gene. Because of considerable tumor bulk in the neck that was not resectable, the patient underwent partial resection at age 14 years. Since then, the patient has received only suppressive thyroid hormone therapy. He is now 71 years old, which is 57 years after the initial resection. The patient received care at our institution from July 2009 to August 2019, during which we documented the stability of multiple calcified masses in the neck. Follow-up examinations at another institution from September 2019 to April 2023 also confirmed the stability of the masses. The underlying cause of this unusually long indolent course of the disease is unclear. Whether extensive tumor calcifications or the MYH11 sequence variation contributed to the disease course is also uncertain.

Learning points

• Papillary thyroid cancer with neck metastases may, in some cases, be stable and remain asymptomatic for decades.

• If locoregional stability of papillary thyroid cancer is documented for many years, observation may be preferable to extensive neck surgery in selected cases.

• This is the first report of an MYH11 gene alteration and thoracic aortic aneurysm in a patient with papillary thyroid cancer with indolent neck metastases.

• Future studies of MYH11 gene alterations in thyroid carcinoma are needed.

Summary

IgG4-related disease is a multiorgan disorder in which nodules and hypertrophic lesions are observed simultaneously, or separately, in areas including the pancreas, liver, lungs, salivary glands, thyroid glands, and pituitary glands. IgG4-related hypophysis is one of several IgG4-related diseases and is characterized by pituitary gland and pituitary stalk thickening, various degrees of hypopituitarism, and increased serum IgG4 levels. Steroid therapy is effective for patients with IgG4-related hypophysis, but the reported effectiveness of steroid therapy for restoring pituitary function differs between studies. Following an episode of autoimmune pancreatitis 10 years prior, enlargement of the pituitary gland and stalk along with panhypopituitarism and polyuria developed in a 73-year-old male. A high serum IgG4 level and biopsy of the submandibular gland showing infiltration of IgG4-positive plasma cells led to a clinical diagnosis of IgG4-related hypophysitis. Prednisolone treatment reduced the swelling of the pituitary gland and stalk and improved anterior pituitary function. Although arginine vasopressin secretion remained insufficient, polyuria was relieved and kept in remission even after prednisolone treatment was completed. This is the first reported case in which prednisolone was able to maintain both normal anterior pituitary function and remission of polyuria caused by IgG4-related hypophysitis. IgG4-related hypophysitis has previously been associated with a relapse of symptoms during treatment. However, the patient reported in this case study remained in remission for over 3 months after completion of steroid treatment and should be monitored closely for changes in pituitary function.

Learning points

• Steroid therapy is the first-line therapy for pituitary dysfunction and pituitary stalk swelling in IgG4-related hypophysitis.

• In this case, although posterior pituitary function remained insufficient, polyuria was relieved and kept in remission for over 3 months even after prednisolone treatment was completed.

• IgG4-related hypophysitis has been associated with the relapse of symptoms during steroid tapering, and changes in pituitary function and symptoms should be monitored closely.

• When we encounter cases of adrenal insufficiency and polyuria during observation of autoimmune pancreatitis or other IgG4-related disease, we should consider the possibility of IgG4-related hypophysitis in mind.

Summary

A 73-year-old woman with type 2 diabetes mellitus was referred to our department for glycaemic control. Physical examination revealed two subcutaneous hard masses around the left shoulder and the right hip joint. The patient could not fully extend her fingers because of skin sclerosis in both hands. Laboratory studies showed hyperphosphataemia and a high ratio of renal tubular maximum reabsorption of phosphate to glomerular filtration rate. There were no abnormalities in serum calcium, creatinine, alkaline phosphatase, and intact parathyroid hormone levels, whereas serum fibroblast growth factor 23 was low. Hyperphosphataemic familial tumoural calcinosis/hyperostosis-hyperphosphataemia syndrome (HFTC/HHS) was diagnosed using whole genome sequencing that revealed a novel frameshift beyond the 584th threonine located in the lectin domain of UDP-N-acetyl-alpha-D-galactosamine:polypeptide N-acetylgalactosaminyltransferase 3 associated with a duplication of the 1748th thymine in the coding region of the corresponding gene. Furthermore, anti-nuclear, anti-centromere, and anti-cardiolipin antibodies were positive, implying that comorbid limited type scleroderma might play a role in tumoural calcinosis (TC) development. A low phosphate diet was prescribed with phosphate-lowering medications, including aluminium hydroxide, acetazolamide, and sevelamer hydrochloride. The patient displayed a decrease in serum phosphate levels from 6.5 to 5.5 mg/dL 10 months after the initiation of treatment, but her TC had not improved during treatment for more than 1 year. This case was interesting because the patient with HFTC/HHS exhibited TC despite being over her 60s, and subsequent scleroderma might contribute to the specific clinical course. When HFTC/HHS presents with elderly-onset TC, the involvement of comorbidities in exacerbating TC should be considered.

Learning points

• HFTC/HHS occurs on an autosomal recessive basis, but its clinical course and manifestations differ significantly throughout the cases.

• HFTC/HHS may be undiagnosed until later in life because of its rarity, unfamiliarity, and phenotype diversity; therefore, HFTC/HHS should be included in the differential diagnosis of elderly patients with unexplained hyperphosphataemia or ectopic calcinosis.

• Comorbidities, including rheumatologic disorders, may contribute to developing HFTC/HHS-associated calcinosis.

Summary

We report a 61-year-old male patient without personal history of thyroid carcinoma or radiation exposure. In 2011, he presented with a cervical mass whose biopsy diagnosed a papillary thyroid carcinoma (PTC) in a lymph node metastasis (LNM). Total thyroidectomy with lymphadenectomy of central and ipsilateral compartment was performed. Histopathology identified a 2 mm follicular variant of PTC and LNM in 25/25 lymph nodes. The patient was treated with 150 mCi of radioactive iodine (RAI), followed by levothyroxine suppressive therapy. In 2016, a retrotracheal mass was diagnosed, suggesting local recurrence; patient was submitted to surgical excision and RAI therapy (120 mCi). Due to seizures, in 2019, a brain CT was performed that diagnosed brain metastases. The patient underwent debulking of the main lesion. Histopathology analysis confirmed a metastatic lesion with variated morphology: classical PTC and follicular pattern and hobnail and tall cell features. Molecular analysis revealed BRAFV600E in LNM at presentation and BRAFV600E and TERT promoter (TERTp) mutations in the recurrent LNM and brain metastasis. Based upon this experience we review the reported cases of subcentimetric PTC with brain metastases and discuss the molecular progression of the present case.

Learning points

• Papillary microcarcinoma (PMCs) usually have very good prognosis with low impact on patient survival.

• PMCs presenting in elderly patients with LNM at diagnosis may carry a guarded outcome.

• Brain metastasis although rare indicate aggressive phenotypic features.

• Patient risk stratification of PMCs based on histopathological analysis and genetic testing may have a significant impact on prognosis providing therapeutic markers, that may predict disease progression and overall outcome.