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Andreia Amado Centro Hospitalar Vila Nova de Gaia/Espinho, Portugal, R. Conceição Fernandes S/N, 4434-502 Vila Nova de Gaia, Portugal

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Elisabete Teixeira i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, R. Alfredo Allen 208, 4200-135 Porto, Portugal
IPATIMUP - Instituto de Patologia e Imunologia Molecular da Universidade do Porto, Rua Júlio Amaral de Carvalho 45, 4200-135 Porto, Portugal
Faculdade de Medicina da Universidade do Porto, Alameda Prof. Hernâni Monteiro, 4200-319 Porto, Portugal

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Sule Canberk i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, R. Alfredo Allen 208, 4200-135 Porto, Portugal
IPATIMUP - Instituto de Patologia e Imunologia Molecular da Universidade do Porto, Rua Júlio Amaral de Carvalho 45, 4200-135 Porto, Portugal
Faculdade de Medicina da Universidade do Porto, Alameda Prof. Hernâni Monteiro, 4200-319 Porto, Portugal

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Sofia Macedo i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, R. Alfredo Allen 208, 4200-135 Porto, Portugal
IPATIMUP - Instituto de Patologia e Imunologia Molecular da Universidade do Porto, Rua Júlio Amaral de Carvalho 45, 4200-135 Porto, Portugal
Instituto de Ciências Biomédicas de Abel Salazar, Universidade do Porto, R. Jorge de Viterbo Ferreira 228, 4050-313 Porto, Portugal

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Bárbara Castro Centro Hospitalar Vila Nova de Gaia/Espinho, Portugal, R. Conceição Fernandes S/N, 4434-502 Vila Nova de Gaia, Portugal

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Hugo Pereira Centro Hospitalar Vila Nova de Gaia/Espinho, Portugal, R. Conceição Fernandes S/N, 4434-502 Vila Nova de Gaia, Portugal

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João Varanda Centro Hospitalar Vila Nova de Gaia/Espinho, Portugal, R. Conceição Fernandes S/N, 4434-502 Vila Nova de Gaia, Portugal

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Susana Graça Centro Hospitalar Vila Nova de Gaia/Espinho, Portugal, R. Conceição Fernandes S/N, 4434-502 Vila Nova de Gaia, Portugal

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Amélia Tavares Centro Hospitalar Vila Nova de Gaia/Espinho, Portugal, R. Conceição Fernandes S/N, 4434-502 Vila Nova de Gaia, Portugal
i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, R. Alfredo Allen 208, 4200-135 Porto, Portugal
IPATIMUP - Instituto de Patologia e Imunologia Molecular da Universidade do Porto, Rua Júlio Amaral de Carvalho 45, 4200-135 Porto, Portugal
Faculdade de Medicina da Universidade do Porto, Alameda Prof. Hernâni Monteiro, 4200-319 Porto, Portugal

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Carlos Soares Centro Hospitalar Vila Nova de Gaia/Espinho, Portugal, R. Conceição Fernandes S/N, 4434-502 Vila Nova de Gaia, Portugal

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Maria João Oliveira Centro Hospitalar Vila Nova de Gaia/Espinho, Portugal, R. Conceição Fernandes S/N, 4434-502 Vila Nova de Gaia, Portugal

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Manuel Oliveira Centro Hospitalar Vila Nova de Gaia/Espinho, Portugal, R. Conceição Fernandes S/N, 4434-502 Vila Nova de Gaia, Portugal

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Paula Soares i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, R. Alfredo Allen 208, 4200-135 Porto, Portugal
IPATIMUP - Instituto de Patologia e Imunologia Molecular da Universidade do Porto, Rua Júlio Amaral de Carvalho 45, 4200-135 Porto, Portugal
Faculdade de Medicina da Universidade do Porto, Alameda Prof. Hernâni Monteiro, 4200-319 Porto, Portugal

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Manuel Sobrinho Simões i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, R. Alfredo Allen 208, 4200-135 Porto, Portugal
IPATIMUP - Instituto de Patologia e Imunologia Molecular da Universidade do Porto, Rua Júlio Amaral de Carvalho 45, 4200-135 Porto, Portugal
Faculdade de Medicina da Universidade do Porto, Alameda Prof. Hernâni Monteiro, 4200-319 Porto, Portugal
Centro Hospitalar Universitário São João, Porto, Alameda Prof. Hernâni Monteiro, 4200-319 Porto, Portugal

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Antónia Afonso Póvoa Centro Hospitalar Vila Nova de Gaia/Espinho, Portugal, R. Conceição Fernandes S/N, 4434-502 Vila Nova de Gaia, Portugal
i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, R. Alfredo Allen 208, 4200-135 Porto, Portugal
IPATIMUP - Instituto de Patologia e Imunologia Molecular da Universidade do Porto, Rua Júlio Amaral de Carvalho 45, 4200-135 Porto, Portugal
Faculdade de Medicina da Universidade do Porto, Alameda Prof. Hernâni Monteiro, 4200-319 Porto, Portugal

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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.

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Valentim Lopes Hospital de Braga, EPE, Portugal

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Catarina Machado Hospital de Braga, EPE, Portugal

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Adriana De Sousa Lages Hospital de Braga, EPE, Portugal
Faculdade de Medicina, Universidade de Coimbra, Portugal

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Summary

We report a case of a woman with a diagnosis of breast cancer who unintentionally started gaining weight, feeling tired, and constipated 44 weeks after the initiation of trastuzumab. Hypothyroidism secondary to an autoimmune thyroiditis associated with trastuzumab was diagnosed, the first case described in Portugal and the fourth case described worldwide. Our intention regarding the publication of this case report is to alert the clinicians treating people with trastuzumab that they should ask the patients about symptoms of hypothyroidism and should screen the thyroid function of the patients before, during, and after the initiation of trastuzumab.

Learning points

  • Trastuzumab is a humanized MAB used in HER2-positive breast and gastric cancer.

  • Trastuzumab-associated autoimmune thyroid disease (AITD) is rare (incidence rate in an RCT of 0.3%).

  • Manifestations of autoimmune thyroiditis associated with trastuzumab resemble those of hypothyroidism in other clinical contexts, but the presence of goiter is highlighted as a reason for medical evaluation. Biochemically, it is characterized by an increased thyroid-stimulating hormone (TSH) with or without a low FT4/FT3, and sonographically with a pattern of thyroiditis.

  • The treatment consists of levothyroxine, in a dose of 1.6–1.8 µg/kg/day, with re-evaluation of the thyroid function in 4–6 weeks.

  • We report the first case of autoimmune thyroiditis secondary to trastuzumab in Portugal.

  • It is important to evaluate the thyroid function before, during, and after the initiation of this therapeutic agent.

Open access
Bruno Bouça Department of Endocrinology, Diabetes and Metabolism - Centro Hospitalar Universitário de Lisboa Central, Lisbon, Portugal
Nova Medical School/ Faculdade de Ciencias Medicas, Universidade Nova de Lisboa, Lisbon, Portugal

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Mariana Cascão Intensive Care Unit - Centro Hospitalar Universitário de Lisboa Central, Lisbon, Portugal

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Pedro Fiúza Department of Internal Medicine, Unit 7.2 - Centro Hospitalar Universitário de Lisboa Central, Lisbon, Portugal

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Sara Amaral Department of Endocrinology, Diabetes and Metabolism - Centro Hospitalar Universitário de Lisboa Central, Lisbon, Portugal
Nova Medical School/ Faculdade de Ciencias Medicas, Universidade Nova de Lisboa, Lisbon, Portugal

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Paula Bogalho Department of Endocrinology, Diabetes and Metabolism - Centro Hospitalar Universitário de Lisboa Central, Lisbon, Portugal
Nova Medical School/ Faculdade de Ciencias Medicas, Universidade Nova de Lisboa, Lisbon, Portugal

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José Silva-Nunes Department of Endocrinology, Diabetes and Metabolism - Centro Hospitalar Universitário de Lisboa Central, Lisbon, Portugal
Nova Medical School/ Faculdade de Ciencias Medicas, Universidade Nova de Lisboa, Lisbon, Portugal
Health and Technology Research Center (H&TRC), Escola Superior de Tecnologia da Saude de Lisboa, Lisbon, Portugal

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Summary

17-Alpha-hydroxylase deficiency (17OHD) is a rare autosomal recessive disease, representing 1% of cases of congenital adrenal hyperplasia. A 44-year-old female presented to the emergency department complaining of generalized asthenia and polyarthralgia for about 2 weeks. On examination, she was hypertensive (174/100 mmHg), and laboratory results revealed hypokalemia and hypocortisolism. She had an uncharacteristic morphotype, BMI of 16.7 kg/m2, cutaneous hyperpigmentation, and Tanner stage M1P1, with normal female external genitalia. She reported to have primary amenorrhea. Further analytical evaluations of her hormone levels were performed CT scan revealed adrenal bilateral hyperplasia and absence of female internal genitalia. A nodular lesion was observed in the left inguinal canal with 25 × 10 mm, compatible with a testicular remnant. Genetic analysis identified the c.3G>A p.(Met1?) variant in homozygosity in the CYP17A1 gene, classified as pathogenic, confirming the diagnosis of 17OHD. Karyotype analysis was compatible with 46,XY. The association of severe hypokalemia, hypertension, hypocortisolism, and oligo/amenorrhea and the absence of secondary sexual characteristics favored the diagnosis of 17OHD, confirmed by genetic testing. As in other published clinical cases, diagnosis outside pediatric age is not rare and should be considered when severe hypokalemia occurs in hypertensive adults with a lack of secondary sexual characteristics.

Learning points

  • The association of severe hypokalemia, hypertension, hypocortisolism, and oligo/amenorrhea and the absence of secondary sexual characteristics favor the diagnosis of 17-alpha-hydroxylase deficiency (17OHD).

  • Diagnosis outside pediatric age is not rare.

  • 17OHD should be considered when severe hypokalemia occurs in hypertensive adults with a lack of secondary sexual characteristics.

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Clara Cunha Department of Endocrinology, Hospital Egas Moniz, Lisbon, Portugal

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Filipa Mousinho Department of Haematology, Hospital São Francisco Xavier, Lisbon, Portugal

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Catarina Saraiva Department of Endocrinology, Hospital Egas Moniz, Lisbon, Portugal

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João Sequeira Duarte Department of Endocrinology, Hospital Egas Moniz, Lisbon, Portugal

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Summary

Primary thyroid lymphoma (PTL) is a rare malignancy, accounting for less than 5% of all thyroid neoplasms. The follicular subtype is even more rare, accounting for approximately 10% of all PTL cases. We report a case of a 64-year-old woman, who presented with a rapidly growing goitre with mass effect and B symptoms. She had a history of Hashimoto’s thyroiditis and her thyroid ultrasound revealed diffuse goitre with a dominant nodule (56 × 63 × 60 mm) within the right thyroid lobe. Ultrasound-guided percutaneous fine-needle aspiration of the right thyroid nodule was classified as benign, according to Bethesda System, with lymphocytic thyroiditis. A CT scan of the neck showed diffuse enlargement of the thyroid gland extending towards the anterior mediastinum with tracheal deviation and lymphadenopathy within levels VII and right II–IV. The core needle biopsy of the right thyroid nodule revealed a follicular non-Hodgkin’s B cell lymphoma with a Ki67 of 60%. According to the Ann Arbor staging system, she was at stage IIIE. She underwent chemotherapy with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) with remarkable clinical improvement and is currently in remission 2 years after the diagnosis. PTL is an extremely rare malignancy that usually arises in a lymphocytic thyroiditis background, presenting as a rapidly enlarging goitre, which can lead to compressive symptoms or airway comprise.

Learning points

  • Primary thyroid lymphoma (PTL) is a rare malignancy, accounting for less than 5% of thyroid neoplasms.

  • PTL should be suspected when a patient presents with a rapidly enlarging goitre, especially in the setting of Hashimoto’s thyroiditis.

  • Fine-needle aspiration has a limited capacity for PTL diagnosis due to similar cytomorphological features of lymphoma with thyroiditis. Therefore, in case of clinical suspicion and if fine needle aspiration fails to diagnose PTL, a tissue biopsy should be performed.

  • Treatment is dependent on both the stage and histology of PTL. Chemotherapy and local radiotherapy remain the mainstay treatment for PTL.

Open access
Inês Henriques Vieira Department of Endocrinology, Diabetes and Metabolism, Centro Hospitalar e Universitario de Coimbra EPE, Coimbra, Portugal

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Nádia Mourinho Bala Department of Endocrinology, Diabetes and Metabolism, Hospital Beatriz Ângelo, Loures, Portugal

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Fabiana Ramos Department of Medical Genetics, Diabetes and Growth, Centro Hospitalar e Universitario de Coimbra EPE, Coimbra, Portugal

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Isabel Dinis Department of Endocrinology, Diabetes and Growth, Centro Hospitalar e Universitario de Coimbra EPE, Coimbra, Portugal

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Rita Cardoso Department of Endocrinology, Diabetes and Growth, Centro Hospitalar e Universitario de Coimbra EPE, Coimbra, Portugal

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Joana Serra Caetano Department of Endocrinology, Diabetes and Growth, Centro Hospitalar e Universitario de Coimbra EPE, Coimbra, Portugal

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Dírcea Rodrigues Department of Endocrinology, Diabetes and Metabolism, Centro Hospitalar e Universitario de Coimbra EPE, Coimbra, Portugal

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Isabel Paiva Department of Endocrinology, Diabetes and Metabolism, Centro Hospitalar e Universitario de Coimbra EPE, Coimbra, Portugal

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Alice Mirante Department of Endocrinology, Diabetes and Growth, Centro Hospitalar e Universitario de Coimbra EPE, Coimbra, Portugal

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Summary

Congenital isolated adrenocorticotrophic hormone (ACTH) deficiency due to T-box transcription factor-19 (TBX19 mutation) (MIM 201400; ORPHA 199296) usually presents in the neonatal period with severe hypoglycemia, seizures, and sometimes prolonged cholestatic jaundice. We report a case with an unusual presentation that delayed the diagnosis. A 9-month-old female patient with no relevant personal history was admitted to the emergency department due to a hypoglycemic seizure in the context of acute gastroenteritis. There was rapid recovery after glucose administration. At age 4, she presented with tonic-clonic seizures, fever, and gastrointestinal symptoms and came to need support in an intensive care unit. Low serum cortisol was documented and hydrocortisone was initiated. After normalization of inflammatory parameters, the patient was discharged with hydrocortisone. The genetic investigation was requested and compound heterozygous mutations in TBX19 were detected. This is a rare case of presentation of TBX19 mutation outside the neonatal period and in the setting of acute disease, which presented a diagnostic challenge.

Learning points

  • Congenital isolated adrenocorticotrophic hormone deficiency due to TBX19 mutation usually presents with neonatal hypoglycemia and prolonged cholestatic jaundice.

  • An uneventful neonatal period, however, does not exclude the diagnosis as the disease may be asymptomatic at this stage.

  • In the context of idiopathic hypoglycemia, even in the context of acute disease, hypocortisolism must always be excluded.

  • Genetic evaluation should be performed in cases of congenital central hypocortisolism to allow proper counselling.

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Carolina Chaves Department of Endocrinology and Nutrition, Hospital Divino Espírito Santo de Ponta Delgada, EPER, Azores Islands, Portugal

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Teresa Kay Department of Medical Genetics, Hospital Dona Estefânia, Centro Hospitalar de Lisboa Central, EPE, Lisbon, Portugal

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João Anselmo Department of Endocrinology and Nutrition, Hospital Divino Espírito Santo de Ponta Delgada, EPER, Azores Islands, Portugal

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Summary

Leptin is secreted by adipocytes in response to fat storage and binds to its receptor (LEPR), which is ubiquitously expressed throughout the body. Leptin regulates energy expenditure and is anorexigenic. In this study, we describe the clinical and hormonal findings of three siblings with a personal history of rapid weight gain during the first months of life. They had delayed puberty, high levels of FSH (15.6 ± 3.7 mUI/mL; reference: 1.5–12.4) and LH (12.3 ± 2.2 mUI/mL; reference: 1.7–8.6), normal oestradiol and total testosterone and successful fertility. None of the patients had dyslipidemia, diabetes or thyroid disease. Next-generation sequencing identified a pathogenic homozygous variant c.2357T>C, p.(Leu786Pro) in LEPR. Their parents and children were heterozygous for this mutation. We compared clinical and biochemical findings of homozygous carriers with first-degree heterozygous family members and ten randomly selected patients with adult-onset morbid obesity. Homozygous carriers of the mutation had significantly higher BMI (32.2 ± 1.7 kg/m2 vs 44.5 ± 7.1 kg/m2, P = 0.023) and increased serum levels of leptin (26.3 ± 9.3 ng/mL vs 80 ± 36.4 ng/mL, P = 0.028) than their heterozygous relatives. Compared with the ten patients with adult-onset morbid obesity, serum levels of leptin were not significantly higher in homozygous carriers (53.8 ± 24.1 ng/mL vs 80 ± 36.4 ng/mL, P = 0.149), and thus serum levels of leptin were not a useful discriminative marker of LEPR mutations. We described a rare three-generation family with monogenic obesity due to a mutation in LEPR. Patients with early onset obesity should be considered for genetic screening, as the identification of mutations may allow personalized treatment options (e.g. MC4R-agonists) and targeted successful weight loss.

Learning points

  • The early diagnosis of monogenic forms of obesity can be of great interest since new treatments for these conditions are becoming available.

  • Since BMI and leptin levels in patients with leptin receptor mutations are not significantly different from those found in randomly selected morbid obese patients, a careful medical history is mandatory to suspect this condition.

  • Loss of leptin receptor function has been associated with infertility. However, our patients were able to conceive, emphasizing the need for genetic counselling in affected patients with this condition.

Open access
Inês Vieira Endocrinology Diabetes and Metabolism Department of Coimbra Hospital and Universitary Centre, Coimbra, Portugal

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Sofia Lopes Endocrinology Diabetes and Metabolism Department of Coimbra Hospital and Universitary Centre, Coimbra, Portugal

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Margarida Bastos Endocrinology Diabetes and Metabolism Department of Coimbra Hospital and Universitary Centre, Coimbra, Portugal

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Luísa Ruas Endocrinology Diabetes and Metabolism Department of Coimbra Hospital and Universitary Centre, Coimbra, Portugal

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Dírcea Rodrigues Endocrinology Diabetes and Metabolism Department of Coimbra Hospital and Universitary Centre, Faculty of Medicine of the University of Coimbra, Coimbra, Portugal

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Isabel Paiva Endocrinology Diabetes and Metabolism Department of Coimbra Hospital and Universitary Centre, Coimbra, Portugal

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Summary

The coexistence of neurofibromatosis type 1 (NFT1) and Turner syndrome (TS) has only been reported in a few patients and may represent a diagnostic challenge. We describe the case of a 16-year-old girl, with a prior clinical diagnosis of NFT1, who was referred to Endocrinology appointments for the etiological study of primary amenorrhea. Evaluation of the anterior pituitary function was requested and hypergonadotropic hypogonadism was detected. During the etiological study, a 45X karyotype was found and TS was diagnosed. The fact that NFT1 can also be associated with short stature, short broad neck and hypertelorism was likely responsible for TS being diagnosed in late adolescence. As both TS and NFT1 are relatively common genetic disorders, it is important to be alert to the possibility that the presence of one disease does not invalidate the other.

Learning points

  • The concomitant presence of two syndromes in the same patient is unlikely and represents a diagnostic challenge.

  • Some phenotypic characteristics and clinical manifestations may be shared by several syndromes.

  • Some syndromes, such as neurofibromatosis type 1 may have very heterogeneous presentations.

  • It is important to be alert to the characteristics that are not explained by the initial diagnosis.

  • If such features are present, diagnostic work-up must be performed regardless of the initial syndromic diagnosis.

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Clara Cunha Department of Endocrinology Hospital Egas Moniz, Lisbon, Portugal

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Eugénia Silva Department of Endocrinology Hospital Egas Moniz, Lisbon, Portugal

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Ana Cláudia Vieira Department of Pneumology, Hospital Egas Moniz, Lisbon, Portugal

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Catarina Saraiva Department of Endocrinology Hospital Egas Moniz, Lisbon, Portugal

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Sequeira Duarte Department of Endocrinology Hospital Egas Moniz, Lisbon, Portugal

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Summary

Immunotherapy has become an important pillar for the management of advanced cancer. Immune-related adverse events including endocrinopathies have been well described with programmed cell death 1 inhibitors such as pembrolizumab. While thyroid dysfunction is the most common endocrinopathy associated with pembrolizumab, new-onset autoimmune diabetes mellitus (DM) is extremely rare. The authors report a case of pembrolizumab-induced primary hypothyroidism and type 1 diabetes mellitus presenting with diabetic ketoacidosis (DKA). A 59-year-old female patient was treated with pembrolizumab for a stage 4 lung adenocarcinoma. She presented to the emergency department with hyperglycaemia-related signs and symptoms, such as polyuria, polydipsia, weight loss, vomiting, asthenia and dehydration, 3 weeks after her first dose of pembrolizumab. Laboratory evaluation revealed hyperglycaemia, hyperketonaemia and high anion gap metabolic acidaemia consistent with DKA. After prompt and adequate treatment of DKA, she transitioned to s.c. basal-bolus insulin. The diagnose of autoimmune DM was established based on the undetectable C-peptide levels and seropositivity for antiglutamic acid decarboxylase antibodies. Additional hormonal parameters revealed overt hypothyroidism and levothyroxine therapy was initiated. This case highlights the importance of blood glucose and thyroid function monitoring as an integral part of cancer treatment protocols for pembrolizumab and other immune checkpoint inhibitors.

Learning points

  • Programmed cell death 1 (PD1) inhibitors such as pembrolizumab can cause endocrine immune-related adverse events (irAE), including thyroid dysfunction and type 1 diabetes mellitus (T1DM).

  • Thyroid dysfunction is the most frequent endocrine irAE secondary to PD1 inhibitors.

  • Autoimmune diabetes and possible resultant diabetic ketoacidosis are rare, but life-threatening adverse events associated with pembrolizumab.

  • Pembrolizumab-induced T1DM often present with relatively low HbAlc levels, reflecting the fulminant onset of β-cell destruction.

  • Patients treated with pembrolizumab and other immune checkpoints inhibitors should be monitored regularly for hyperglycaemia and thyroid dysfunction.

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Diana Festas Silva Endocrinology, Diabetes and Metabolism Department, Coimbra Hospital and University Centre, Coimbra, Portugal

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Adriana De Sousa Lages Faculty of Medicine of the University of Coimbra, Coimbra, Portugal
Endocrinology Department, Braga Hospital, Braga, Portugal

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Joana Serra Caetano Pediatric Endocrinology, Diabetes and Growth Department, Coimbra Pediatric Hospital, Coimbra, Portugal

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Rita Cardoso Pediatric Endocrinology, Diabetes and Growth Department, Coimbra Pediatric Hospital, Coimbra, Portugal

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Isabel Dinis Pediatric Endocrinology, Diabetes and Growth Department, Coimbra Pediatric Hospital, Coimbra, Portugal

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Leonor Gomes Endocrinology, Diabetes and Metabolism Department, Coimbra Hospital and University Centre, Coimbra, Portugal
Faculty of Medicine of the University of Coimbra, Coimbra, Portugal

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Isabel Paiva Endocrinology, Diabetes and Metabolism Department, Coimbra Hospital and University Centre, Coimbra, Portugal

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Alice Mirante Pediatric Endocrinology, Diabetes and Growth Department, Coimbra Pediatric Hospital, Coimbra, Portugal

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Summary

Hypoparathyroidism is characterized by low or inappropriately normal parathormone production, hypocalcemia and hyperphosphatemia. Autosomal dominant hypocalcemia (ADH) type 1 is one of the genetic etiologies of hypoparathyroidism caused by heterozygous activating mutations in the calcium-sensing receptor (CASR) gene. Current treatments for ADH type 1 include supplementation with calcium and active vitamin D. We report a case of hypoparathyroidism in an adolescent affected by syncope without prodrome. The genetic testing revealed a variant in the CASR gene. Due to standard therapy ineffectiveness, the patient was treated with recombinant human parathyroid hormone (1–34), magnesium aspartate and calcitriol. He remained asymptomatic and without neurological sequelae until adulthood. Early diagnosis and treatment are important to achieve clinical stability.

Learning points

  • Autosomal dominant hypocalcemia (ADH) type 1 is one of the genetic etiologies of hypoparathyroidism caused by heterozygous activating mutations in the calcium-sensing receptor (CASR) gene.

  • The variant c.368T>C (p.Leu123Ser) in heterozygosity in the CASR gene is likely pathogenic and suggests the diagnosis of ADH type 1.

  • Teriparatide (recombinant human parathyroid hormone 1–34) may be a valid treatment option to achieve clinical stability for those individuals whose condition is poorly controlled by current standard therapy.

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Mariana Aveiro-Lavrador Endocrinology, Diabetes and Metabolism Department, Coimbra Hospital and University Center, Coimbra, Portugal

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Adriana De Sousa Lages Endocrinology Department, Braga Hospital, Braga, Portugal

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Luísa Barros Endocrinology, Diabetes and Metabolism Department, Coimbra Hospital and University Center, Coimbra, Portugal

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Isabel Paiva Endocrinology, Diabetes and Metabolism Department, Coimbra Hospital and University Center, Coimbra, Portugal

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Summary

Congenital adrenal hyperplasia (CAH) is a group of autosomal recessive disorders related to enzyme deficiencies in the adrenal steroidogenesis pathway leading to impaired corticosteroid biosynthesis. Depending on the extension of enzyme defect, there may be variable severities of CAH – classic and non-classic. We report the case of a 37-year-old male patient with a previously unknown diagnosis of classic CAH referred to Endocrinology evaluation due to class III obesity and insulin resistance. A high diagnostic suspicion was raised at the first Endocrinology consultation after careful past medical history analysis especially related to the presence of bilateral adrenal myelolipomas and primary infertility. A genetic test confirmed the presence of a variant of the CYP21A2 in homozygous with an enzymatic activity of 0–1%, corresponding to a classic and severe CAH form. Our case represents an unusually late definitive diagnose of classic CAH since the definition was established only during adulthood in the fourth decade of life. The missing diagnosis of classic 21 hydroxylase deficiency during infancy led to important morbidity, with a high impact on patients’ quality of life.

Learning points

  • Congenital adrenal hyperplasia (CAH) refers to a group of autosomal recessive enzyme disorders responsible for an impaired cortical adrenal hormonal synthesis.

  • CAH may be divided into two major forms: classic and non-classic CAH.

  • If untreated, CAH may be fatal or may be responsible for important multi-organ long-term consequences that can be undervalued during adulthood.

  • Adrenal myelolipomas are associated with chronic exposure to high ACTH levels and continuous androgen hyperstimulation typically found in undertreated CAH patients.

  • Testicular adrenal rest tumours (TART) and primary infertility can be the first manifestation of the disease during adulthood.

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