Differentiated thyroid cancers generally have favorable prognoses, though follicular thyroid cancer is overall associated with a worse prognosis due in part to increased incidence of distant metastasis. We report a case of a 51-year-old woman with a history of widely invasive follicular thyroid carcinoma treated with a total thyroidectomy, radioactive iodine and external beam radiation. Five and a half years following her surgery, she was found to have an axillary lymph node mass, multiple lung masses, and a hilar mass in the setting of declining thyroglobulin (Tg) antibodies. Her metastases were initially thought to be due to a primary lung adenocarcinoma given a neoplastic cell immunophenotype that included an absence of Tg expression and co-expression of TTF-1 and Napsin A. However, PAX8 expression demonstrated that the axillary and hilar metastases were actually thyroid in origin rather than lung. Axillary metastases in differentiated thyroid carcinoma are exceedingly rare and previous reports have typically involved widely disseminated disease with extensive neck lymphadenopathy. With a decline in Tg antibodies levels in high-risk patients, one should consider progression and loss of differentiation of thyroid carcinoma rather than a response to treatment.
Stephanie J Kim, Eric Morris Bomberg, Joshua Menke, Marika Russell, and Elizabeth J Murphy
Sofia Pilar Ildefonso-Najarro, Esteban Alberto Plasencia-Dueñas, Cesar Joel Benites-Moya, Jose Carrion-Rojas, and Marcio Jose Concepción-Zavaleta
Cushing’s syndrome is an endocrine disorder that causes anovulatory infertility secondary to hypercortisolism; therefore, pregnancy rarely occurs during its course. We present the case of a 24-year-old, 16-week pregnant female with a 10-month history of unintentional weight gain, dorsal gibbus, nonpruritic comedones, hirsutism and hair loss. Initial biochemical, hormonal and ultrasound investigations revealed hypokalemia, increased nocturnal cortisolemia and a right adrenal mass. The patient had persistent high blood pressure, hyperglycemia and hypercortisolemia. She was initially treated with antihypertensive medications and insulin therapy. Endogenous Cushing’s syndrome was confirmed by an abdominal MRI that demonstrated a right adrenal adenoma. The patient underwent right laparoscopic adrenalectomy and anatomopathological examination revealed an adrenal adenoma with areas of oncocytic changes. Finally, antihypertensive medication was progressively reduced and glycemic control and hypokalemia reversal were achieved. Long-term therapy consisted of low-dose daily prednisone. During follow-up, despite favorable outcomes regarding the patient’s Cushing’s syndrome, stillbirth was confirmed at 28 weeks of pregnancy. We discuss the importance of early diagnosis and treatment of Cushing’s syndrome to prevent severe maternal and fetal complications.
- Pregnancy can occur, though rarely, during the course of Cushing’s syndrome.
- Pregnancy is a transient physiological state of hypercortisolism and it must be differentiated from Cushing’s syndrome based on clinical manifestations and laboratory tests.
- The diagnosis of Cushing’s syndrome during pregnancy may be challenging, particularly in the second and third trimesters because of the changes in the maternal hypothalamic-pituitary-adrenal axis.
- Pregnancy during the course of Cushing’s syndrome is associated with severe maternal and fetal complications; therefore, its early diagnosis and treatment is critical.
Sakshi Jhawar, Rahul Lakhotia, Mari Suzuki, James Welch, Sunita K Agarwal, John Sharretts, Maria Merino, Mark Ahlman, Jenny E Blau, William F Simonds, and Jaydira Del Rivero
Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant condition characterized by parathyroid, anterior pituitary and enteropancreatic endocrine cell tumors. Neuroendocrine tumors occur in approximately in 5–15% of MEN1 patients. Very few cases of ovarian NETs have been reported in association with clinical MEN1 and without genetic testing confirmation. Thirty-three-year-old woman with MEN1 was found to have right adnexal mass on computed tomography (CT). Attempt at laparoscopic removal was unsuccessful, and mass was removed via a minilaparotomy in piecemeal fashion. Pathology showed ovarian NET arising from a teratoma. Four years later, patient presented with recurrence involving the pelvis and anterior abdominal wall. She was treated with debulking surgery and somatostatin analogs (SSAs). Targeted DNA sequencing analysis on the primary adnexal mass as well as the recurrent abdominal wall tumor confirmed loss of heterozygosity (LOH) at the MEN1 gene locus. This case represents to our knowledge, the first genetically confirmed case of ovarian NET arising by a MEN1 mechanism in a patient with MEN1. Extreme caution should be exercised during surgery as failure to remove an ovarian NET en masse can result in peritoneal seeding and recurrence. For patients with advanced ovarian NETs, systemic therapy options include SSAs, peptide receptor radioligand therapy (PRRT) and novel agents targeting mammalian target of rapamycin (mTOR) and vascular endothelial growth factor (VEGF).
- Ovarian NET can arise from a MEN1 mechanism, and any adnexal mass in a MEN1 patient can be considered as a possible malignant NET.
- Given the rarity of this disease, limited data are available on prognostication and treatment. Management strategies are extrapolated from evidence available in NETs from primaries of other origins.
- Care should be exercised to remove ovarian NETs en bloc as failure to do so may result in peritoneal seeding and recurrence.
- Treatment options for advanced disease include debulking surgery, SSAs, TKIs, mTOR inhibitors, PRRT and chemotherapy.
Kewan Hamid, Neha Dayalani, Muhammad Jabbar, and Elna Saah
A 6-year-old female presented with chronic intermittent abdominal pain for 1 year. She underwent extensive investigation, imaging and invasive procedures with multiple emergency room visits. It caused a significant distress to the patient and the family with multiple missing days at school in addition to financial burden and emotional stress the child endured. When clinical picture was combined with laboratory finding of macrocytic anemia, a diagnosis of hypothyroidism was made. Although chronic abdominal pain in pediatric population is usually due to functional causes such as irritable bowel syndrome, abdominal migraine and functional abdominal pain. Hypothyroidism can have unusual presentation including abdominal pain. The literature on abdominal pain as the main presentation of thyroid disorder is limited. Pediatricians should exclude hypothyroidism in a patient who presents with chronic abdominal pain. Contrast to its treatment, clinical presentation of hypothyroidism can be diverse and challenging, leading to a delay in diagnosis and causing significant morbidity.
- Hypothyroidism can have a wide range of clinical presentations that are often nonspecific, which can cause difficulty in diagnosis.
- In pediatric patients presenting with chronic abdominal pain as only symptom, hypothyroidism should be considered by the pediatricians and ruled out.
- In pediatric population, treatment of hypothyroidism varies depending on patients’ weight and age.
- Delay in diagnosis of hypothyroidism can cause significant morbidity and distress in pediatrics population.
Tess Jacob, Renee Garrick, and Michael D Goldberg
Metformin is recommended as the first-line agent for the treatment of type 2 diabetes. Although this drug has a generally good safety profile, rare but potentially serious adverse effects may occur. Metformin-associated lactic acidosis, although very uncommon, carries a significant risk of mortality. The relationship between metformin accumulation and lactic acidosis is complex and is affected by the presence of comorbid conditions such as renal and hepatic disease. Plasma metformin levels do not reliably correlate with the severity of lactic acidosis. We present a case of inadvertent metformin overdose in a patient with both renal failure and hepatic cirrhosis, leading to two episodes of lactic acidosis and hypoglycemia. The patient was successfully treated with hemodialysis both times and did not develop any further lactic acidosis or hypoglycemia, after the identification of metformin tablets accidentally mixed in with his supply of sevelamer tablets. Early initiation of renal replacement therapy is key in decreasing lactic acidosis-associated mortality.
- When a toxic ingestion is suspected, direct visualization of the patient’s pills is advised in order to rule out the possibility of patient- or pharmacist-related medication errors.
- Though sending a specimen for determination of the plasma metformin concentration is important when a metformin-treated patient with diabetes presents with lactic acidosis, complex relationships exist between metformin accumulation, hyperlactatemia and acidosis, and the drug may not always be the precipitating factor.
- Intermittent hemodialysis is recommended as the first-line treatment for metformin-associated lactic acidosis (MALA).
- An investigational delayed-release form of metformin with reduced systemic absorption may carry a lower risk for MALA in patients with renal insufficiency, in whom metformin therapy may presently be contraindicated.
Alex González Bóssolo, Michelle Mangual Garcia, Paula Jeffs González, Miosotis Garcia, Guillermo Villarmarzo, and Jose Hernán Martinez
Classical papillary thyroid microcarcinoma (PTMC) is a variant of papillary thyroid carcinoma (PTC) known to have excellent prognosis. It has a mortality of 0.3%, even in the presence of distance metastasis. The latest American Thyroid Association guidelines state that although lobectomy is acceptable, active surveillance can be considered in the appropriate setting. We present the case of a 37-year-old female with a history of PTMC who underwent surgical management consisting of a total thyroidectomy. Although she has remained disease-free, her quality of life has been greatly affected by the sequelae of this procedure. This case serves as an excellent example of how first-line surgical treatment may result more harmful than the disease itself.
- Papillary thyroid microcarcinoma (PTMC) has an excellent prognosis with a mortality of less than 1% even with the presence of distant metastases.
- Active surveillance is a reasonable management approach for appropriately selected patients.
- Patients should be thoroughly oriented about the risks and benefits of active surveillance vs immediate surgical treatment. This discussion should include the sequelae of surgery and potential impact on quality of life, especially in the younger population.
- More studies are needed for stratification of PTMC behavior to determine if conservative management is adequate for all patients with this specific disease variant.
Marta Araujo Castro, Ainhoa Abad López, Luz Martín Fragueiro, and Nuria Palacios García
The 85% of cases of primary hyperparathyroidism (PHPT) are due to parathyroid adenomas (PA) and less than 1% to parathyroid carcinomas (PC). The PA usually measure <2 cm, weigh <1 g and generate a mild PHPT, whereas the PC usually exceeds these dimensions and are associated with a severe PHPT. However, giant PA (GPA), which is defined as those larger than 3 g, has been documented. Those may be associated with very high levels of PTH and calcium. In these cases, their differentiation before and after surgery with PC is very difficult. We present a case of severe PHPT associated with a large parathyroid lesion, and we discuss the differential aspects between the GPA and PC.
- In parathyroid lesions larger than 2 cm, the differential diagnosis between GPA and PC should be considered.
- Pre and postsurgical differentiation between GPA and PC is difficult; however, there are clinical, analytical and radiographic characteristics that may be useful.
- The depth/width ratio larger or smaller than 1 seems to be the most discriminatory ultrasound parameter for the differential diagnosis.
- Loss of staining for parafibromin has a specificity of 99% for the diagnosis of PC.
- The simultaneous presence of several histological characteristics, according to the classification of Schantz and Castleman, is frequent in PC and rare in GPA.
Gemma Xifra, Silvia Mauri, Jordi Gironès, José Ignacio Rodríguez Hermosa, Josep Oriola, Wifredo Ricart, and José Manuel Fernández-Real
Background: Thyroid hormone resistance (RTH) is a rare cause of thyroid dysfunction. High TSH levels, as described in RTH syndrome, are known to be associated with an increased risk of developing thyroid nodules with subsequent growth and malignancy.
Patient findings: In 2006, a 29-year-old Caucasian man presented with a palpable mass in the neck. Increased free thyroxine and triiodothyronine levels were found in the context of unsuppressed TSH levels, despite no signs or symptoms of hyperthyroidism. Ultrasonography revealed a multinodular and enlarged goitre, and fine-needle aspiration cytology revealed suspicious features of malignancy. After excluding pituitary tumour and levothyroxine (l-T4) treatment, the patient was diagnosed with generalized RTH. Screening for all the known mutations in thyroid hormone receptor-β (TR β (THRB)) was negative. Thyroidectomy disclosed five Hürthle adenomas and three hyperplasic nodules. Euthyroidism was achieved after surgery with 6.1 μg/kg per day of l-T4.
Conclusion: RTH may be a risk factor that predisposes to the development of multiple Hürthle cell adenomas. To our knowledge, this is the first case of multiple Hürthle cell adenomas in a patient with RTH.
- High TSH levels, as described in RTH syndrome, are known to be associated with an increased risk of developing thyroid nodules, with subsequent growth and malignancy.
- The exact role of TR β mutants in thyroid carcinogenesis is still undefined.
- We report the first case of multiple Hürthle cell adenomas associated with RTH.
I Huguet, C Lamas, R Vera, A Lomas, R P Quilez, A Grossman, and F Botella
Neuroendocrine tumours (NETs) are a heterogeneous group of neoplasms whose management can be problematic. In many cases, multiple tumours may occur in the same patient or his or her family, and some of these have now been defined genetically, although in other cases the underlying gene or genes involved remain unclear. We describe a patient, a 63-year-old female, who was diagnosed with a medullary thyroid carcinoma (MTC), which was confirmed pathologically after thyroidectomy, but whose circulating calcitonin levels remained elevated after thyroidectomy with no evidence of metastatic disease. Subsequently, an entirely separate and discrete duodenal NET was identified; this was 2.8 cm in diameter and was removed at partial duodenectomy. The tumour stained immunohistochemically for calcitonin, and its removal led to persistent normalisation of the circulating calcitonin levels. There was no germline mutation of the RET oncogene. This is the first identification of a duodenal NET secreting calcitonin and also the first demonstration of a second tumour secreting calcitonin in a patient with MTC. We suggest that where calcitonin levels remain high after removal of a MTC a search for other NETs should be conducted.
- NETs are a complex and heterogeneous group of related neoplasms, and multiple tumours may occur in the same patient.
- Calcitonin can be produced ectopically by several tumours outside the thyroid.
- Persistently elevated calcitonin levels after removal of a MTC may not necessarily indicate persisting or metastatic disease from the tumour.
- The real prevalence of calcitonin-producing NETs may be underestimated, as serum determination is only recommended in the diagnosis of pancreatic NETs.