Diagnostic Challenges of Medullary Thyroid Carcinoma.

BACKGROUND: Medullary thyroid carcinoma (MTC) comprises 1-2% of all thyroid cancers, yet 15% of all thyroid cancer-related deaths. While up to 20% of cases may be predicted due to autosomal dominant germline mutations, 80% of cases are sporadic. However, due to non-specific presenting symptoms and diagnostic imaging, prompt diagnosis and treatment has remained elusive. This article will further investigate the limitations of MTC diagnosis and look into future areas for diagnostic improvement. METHODS: Relevant articles were identified using a systematic PubMed and Google Scholar search. RESULTS: Prophylactic total thyroidectomy for the 20% of MTC cases that are present in autosomal dominant disorder provides definitive treatment. Serum calcitonin (Ctn) screening has several technical limitations due to population variability and laboratory assay interference, but advances in laboratory technology and combined use with fine needle aspiration increase its sensitivity. Other serum assays such as carcinoembryonic antigen and procalcitonin have limited applicability. Thyroid ultrasound remains the gold standard for the initial diagnostic planning, with limited application for CT, MRI, and PET imaging. CONCLUSION: With complete surgical resection the only definitive treatment, early MTC diagnosis has presented an elusive challenge, mainly due to its relative rarity and difficulty in finding an economic screening strategy. Careful family history combined with fine needle aspiration with serum Ctn analysis can improve diagnostic sensitivity and specificity to greater than 95%.

ASSOCIATIONS OF SERUM IONIZED CALCIUM, PHOSPHATE, AND PTH LEVELS WITH PARATHYROID SCAN IN PRIMARY HYPERPARATHYROIDISM.

OBJECTIVE: To evaluate the relationship between various biochemical parameters in patients with primary hyperparathyroidism (PHPT) with positive and negative technetium-99 sestamibi (Tc) parathyroid scans performed with single-photon emission computed tomography/computed tomography (SPECT/CT). METHODS: This retrospective analysis was used to develop a logistic probability model. It included 218 patients with PHPT. The main outcome measures were serum total calcium, ionized calcium, intact parathyroid hormone (PTH), albumin, alkaline phosphatase, phosphate, 25-hydroxy vitamin D, 1,25-dihydroxy vitamin D, 24-h urinary calcium levels, and parathyroid adenoma weight. RESULTS: Individually, using cut-off levels of 6.0 mg/dL for ionized calcium, 3.0 mg/dL for phosphate, and 90 pg/mL for intact PTH, we found that 91.3% ( P = .005), 70.7% ( P = .004) and 87.90% ( P = .023) of the patients had a positive Tc scan with their corresponding strengths of associations in the parentheses. Similar significant associations were sustained in multivariate setting for serum ionized calcium ( P = .015), phosphate ( P = .016), and intact PTH ( P = .028). A logistic probability model was designed to predict the probability of being positive for Tc scan given a set of covariates. CONCLUSION: There are significant associations between the levels of serum ionized calcium, phosphate, intact PTH, and Tc scan positivity. Further studies with larger patient populations are needed. ABBREVIATIONS: BMI = body mass index; CT = computed tomography; CV = coefficient variation; DXA = dual-energy x-ray absorptiometry; MRI = magnetic resonance imaging; PHPT = primary hyperparathyroidism; PPV = positive predictive value; PTH = parathyroid hormone; SPECT = single-photon emission computed tomography; Tc = technetium-99 sestamibi.

Three cases highlighting possible discrepancies in the interpretation of transgender DXA scores.

For diagnosis of osteoporosis, a T-score of ≤-2.5 is recommended for all transgender and gender-diverse patients aged 50 years or older, regardless of hormonal status. This case series presents 3 transgender individuals younger than 50 years undergoing gender-affirming hormone therapy (GAHT) who had DXA scores suggestive of osteoporosis. We highlight possible discrepancies in DXA scan interpretations, especially in forearm bone mineral density measurements. We present the baseline (prior to beginning GAHT), 6-month, and 1-year follow-up DXA data along with pertinent labs to include 25-OH vitamin D, calcium, and alkaline phosphatase, for 2 transgender males (assigned female at birth) and 1 transgender female (assigned male at birth) undergoing GAHT who had low Z-scores and T-scores suggestive of osteoporosis. Multiple studies have analyzed the BMD data of individuals taking GAHT over time, which identify possible causes for low baseline Z-scores for transgender females, but less so for transgender males. Other than positional statements, guidelines remain unclear regarding diagnostic approaches to osteoporosis and low Z-scores in transgender individuals who are premenopausal or under 50 years of age. This case series addresses discrepancies in interpretation that may be encountered by clinicians with baseline and follow-up DXAs, especially involving the forearm, during the course of GAHT. This highlights the importance of establishing clearer guidelines for the diagnosis and treatment of osteoporosis and low BMD for chronological age in the transgender population.

Dental loss, stress fractures, and musculoskeletal pain in a 48-year-old woman.

We report a 48-year-old female patient with various stress fractures of extremities, musculoskeletal pain, and tooth loss. Hypophosphatasia was diagnosed based on clinical and laboratory findings and ALPL genetic results. This case highlights the importance of early diagnosis of hypophosphatasia in adults and appropriate treatment to prevent further complications.

Simultaneous diagnosis of papillary thyroid cancer and systemic mastocytosis.

Key Clinical Message: When managing patients with differentiated thyroid cancers (DTC) and lytic bone lesions, physicians should consider etiologies other than DTC bony metastases when there is no biochemical and functional radiographic evidence of extensive DTC burden. Abstract: Systemic mastocytosis (SM) is a clonal expansion of mast cells associated with an increased risk of solid malignancies. There is no known association between systemic mastocytosis and thyroid cancer. We report a young woman who presented with cervical lymphadenopathy, palpable thyroid nodule, and lytic bone lesions who was diagnosed with papillary thyroid cancer (PTC). The patient's post-surgical thyroglobulin was lower than expected for metastatic thyroid cancer, and the lytic bone lesions did not demonstrate uptake of I123. Upon further evaluation, the patient was found to have SM. We report a case of co-occurrence of PTC and SM.

64-year-old woman • hot flashes, facial flushing, excessive sweating, and palpitations • daily headaches • history of hypertension • Dx?

► hot flashes, facial flushing, excessive sweating, and palpitations ► daily headaches ► history of hypertension.

Dilemmas in the diagnosis and management of osteoporosis in a patient with alkaptonuria: Successful treatment with teriparatide.

Management of osteoporosis in patients with alkaptonuria can be challenging. This is the first case report confirming the effectiveness of teriparatide following zoledronic acid therapy in treating osteoporosis and preventing fragility fractures in a patient with alkaptonuria.

Strategies for improved management of hypothyroidism.

Management is clear-cut-yet many patients don't reach treatment goals. To optimize quality of life, master the fine points of T4 replacement and address the impact of comorbidities.

Coexistence of Cushing Disease With a Solitary Adrenocorticotrophic Hormone-Dependent Adrenal Adenoma.

OBJECTIVE: We report a 49-year-old woman who had minimal features of Cushing syndrome and an incidentally discovered adrenal adenoma. She was subsequently diagnosed with pituitary-dependent Cushing syndrome. METHODS: Laboratory and imaging studies including serum cortisol, plasma adrenocorticotrophic hormone (ACTH), high dose dexamethasone test, corticotropin-releasing hormone test, computed tomography (CT) scan, and magnetic resonance imaging were performed. RESULTS: A 49-year-old woman was admitted for urosepsis. An abdominal CT scan performed during the urosepsis workup showed a 2.7-cm right adrenal adenoma. She denied any abdominal striae or other symptoms. Physical examination showed normal vital signs, minimal facial fullness without central obesity, and striae. Laboratory results were as follows: 24-hour-urine cortisol 294 µg (reference 4.0-50.0), midnight serum cortisol 23.0 µg/dL (reference < 7.5), and plasma ACTH level 39 pg/mL (reference 5-27). A corticotropin-releasing hormone stimulation test showed >20% rise in serum cortisol and >35% rise in ACTH levels. A pituitary magnetic resonance image showed a 5 mm pituitary lesion. The patient underwent transsphenoidal pituitary surgery, which confirmed an ACTH-secreting lesion. Postoperatively, she required hydrocortisone replacement for the next 10 months. A follow-up adrenal CT performed 6 months later showed a decrease in the size of the adrenal adenoma (1.8 cm). CONCLUSION: This case highlights the importance of recognizing the coexistence of ACTH-dependent Cushing disease with an adrenal adenoma and partial ACTH dependency of the adrenal adenoma.

Improvement of depression in a patient with hypothyroidism and deiodinase polymorphism with LT3 Therapy.

We report a 54-year-old man with treatment-resistant depression (TRD) and hypothyroidism who responded to LT3/LT4 combination, rather than LT4 alone. He was able to discontinue all antidepressant medications eventually. Interestingly, the patient has a DIO2 polymorphism.

Graves' disease complicated by concurrent thyroid eye disease and pretibial myxedema successfully treated with teprotumumab.

We report a 51-year-old woman with thyroid eye disease and biopsy-proven pretibial myxedema that was subsequently treated with teprotumumab with improvement.