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Open access

Jonathan Brown and Luqman Sardar

Summary

A 68-year-old previously independent woman presented multiple times to hospital over the course of 3 months with a history of intermittent weakness, vacant episodes, word finding difficulty and reduced cognition. She was initially diagnosed with a TIA, and later with a traumatic subarachnoid haemorrhage following a fall; however, despite resolution of the haemorrhage, symptoms were ongoing and continued to worsen. Confusion screen blood tests showed no cause for the ongoing symptoms. More specialised investigations, such as brain imaging, cerebrospinal fluid analysis, electroencephalogram and serology also gave no clear diagnosis. The patient had a background of hypothyroidism, with plasma thyroid function tests throughout showing normal free thyroxine and a mildly raised thyroid-stimulating hormone (TSH). However plasma anti-thyroid peroxidise (TPO) antibody titres were very high. After discussion with specialists, it was felt she may have a rare and poorly understood condition known as Hashimoto’s encephalopathy (HE). After a trial with steroids, her symptoms dramatically improved and she was able to live independently again, something which would have been impossible at presentation.

Learning points:

  • In cases of subacute onset confusion where most other diagnoses have already been excluded, testing for anti-thyroid antibodies can identify patients potentially suffering from HE.

  • In these patients, and under the guidance of specialists, a trial of steroids can dramatically improve patient’s symptoms.

  • The majority of patients are euthyroid at the time of presentation, and so normal thyroid function tests should not prevent anti-thyroid antibodies being tested for.

  • Due to high titres of anti-thyroid antibodies being found in a small percentage of the healthy population, HE should be treated as a diagnosis of exclusion, particularly as treatment with steroids may potentially worsen the outcome in other causes of confusion, such as infection.

Open access

Kingsley Okolie, Daniel Chen, Raf Ghabrial and Robert Schmidli

Summary

Multinodular goitre is not associated with eye disease, unless in a rare case of Marine–Lenhart syndrome where it coexists with Grave’s disease. Therefore, other causes of exophthalmos need to be ruled out when the eye disease is seen in a patient with multinodular goitre. Confusion can arise in patients with features suggestive of Graves’ ophthalmopathy in the absence of thyroid-stimulating hormone receptor autoantibodies and no evidence of other causes of exophthalmos. We present a case of multinodular goitre in a patient with exophthalmos which flared up after iodine contrast-based study. A 61-year-old Australian presented with a pre-syncopal attack and was diagnosed with toxic multinodular goitre. At the same time of investigations, to diagnose the possible cause of the pre-syncopal attack, computerised tomographic (CT) coronary artery angiogram was requested by a cardiologist. A few days after the iodine contrast-based imaging test was performed, he developed severe eye symptoms, with signs suggestive of Graves’ orbitopathy. MRI of the orbit revealed features of the disease. Although he had pre-existing eye symptoms, they were not classical of thyroid eye disease. He eventually had orbital decompressive surgery. This case poses a diagnostic dilemma of a possible Graves’ orbitopathy in a patient with multinodular goitre.

Learning points:

  • Graves’ orbitopathy can occur in a patient with normal autothyroid antibodies. The absence of the thyroid antibodies does not rule out the disease in all cases.

  • Graves’ orbitopathy can coexist with multinodular goitre.

  • Iodine-based compounds, in any form, can trigger severe symptoms, on the background of Graves’ eye disease.

Open access

H Joshi, M Hikmat, A P Devadass, S O Oyibo and S V Sagi

Summary

IgG4-related disease (IgG4-RD) is an immune-mediated fibro-inflammatory condition which can affect various organs including the pituitary gland. The true annual incidence of this condition remains widely unknown. In addition, it is unclear whether IgG4 antibodies are causative or the end result of a trigger. With no specific biomarkers available, the diagnosis of IgG4-related hypophysitis remains a challenge. Additionally, there is a wide differential diagnosis. We report a case of biopsy-proven IgG4-related hypophysitis in a young man with type 2 diabetes mellitus.

Learning points:

  • IgG4-related hypophysitis is part of a spectrum of IgG4-related diseases.

  • Clinical manifestations result from anterior pituitary hormone deficiencies with or without diabetes insipidus, which can be temporary or permanent.

  • A combination of clinical, radiological, serological and histological evidence with careful interpretation is required to make the diagnosis.

  • Tissue biopsy remains the gold standard investigation.

  • Disease monitoring and long-term management of this condition is a challenge as relapses occur frequently.

Open access

Yoko Olmedilla, Shoaib Khan, Victoria Young, Robin Joseph, Simon Cudlip, Olaf Ansgorge, Ashley Grossman and Aparna Pal

Summary

A 21 year-old woman was found to have a pituitary macroadenoma following an episode of haemophilus meningitis. Biochemical TSH and GH excess was noted, although with no clear clinical correlates. She was treated with a somatostatin analogue (SSA), which restored the euthyroid state and controlled GH hypersecretion, but she re-presented with a further episode of cerebrospinal fluid (CSF) leak and recurrent meningitis. Histology following transsphenoidal adenomectomy revealed a Pit-1 lineage plurihormonal adenoma expressing GH, TSH and PRL. Such plurihormonal pituitary tumours are uncommon and even more unusual to present with spontaneous bacterial meningitis. The second episode of CSF leak and meningitis appears to have been due to SSA therapy-induced tumour shrinkage, which is not a well-described phenomenon in the literature for this type of tumour.

Learning points:

  • Pit-1 lineage GH/TSH/PRL-expressing plurihormonal pituitary adenomas are uncommon. Moreover, this case is unique as the patient first presented with bacterial meningitis.

  • Inmunohistochemical plurihormonality of pituitary adenomas does not necessarily correlate with biochemical and clinical features of hormonal hypersecretion.

  • Given that plurihormonal Pit-1 lineage adenomas may behave more aggressively than classical pituitary adenomas, accurate pathological characterization of these tumours has an increasing prognostic relevance.

  • Although unusual, a CSF leak and meningitis may be precipitated by SSA therapy of a pituitary macroadenoma via tumour shrinkage.

Open access

Anna Tortora, Domenico La Sala and Mario Vitale

Summary

Reduced intestinal absorption of levothyroxine (LT4) is the most common cause of failure to achieve an adequate therapeutic target in hypothyroid patients under replacement therapy. We present the case of a 63-year-old woman with autoimmune hypothyroidism previously well-replaced with tablet LT4 who became unexpectedly no more euthyroid. At presentation, the patient reported the onset of acute gastrointestinal symptoms characterized by nausea, loss of appetite, flatulence, abdominal cramps and diarrhea, associated with increase of thyrotropin levels (TSH: 11 mIU/mL). Suspecting a malabsorption disease, a thyroxine solid-to-liquid formulation switch, at the same daily dose, was adopted to reach an optimal therapeutic target despite the gastrointestinal symptoms persistence. Oral LT4 solution normalized thyroid hormones. Further investigations diagnosed giardiasis, and antibiotic therapy was prescribed. This case report is compatible with a malabsorption syndrome caused by an intestinal parasite (Giardia lamblia). The reduced absorption of levothyroxine was resolved by LT4 oral solution.

Learning points:

  • The failure to adequately control hypothyroidism with oral levothyroxine is a common clinical problem.

  • Before increasing levothyroxine dose in a patient with hypothyroidism previously well-controlled with LT4 tablets but no more in appropriate therapeutic target, we suggest to investigate non adhesion to LT4 therapy, drug or food interference with levothyroxine absorption, intestinal infection, inflammatory intestinal disease, celiac disease, lactose intolerance, short bowel syndrome after intestinal or bariatric surgery, hepatic cirrhosis and congestive heart failure.

  • LT4 oral solution has a better absorptive profile than the tablet. In hypothyroid patients affected by malabsorption syndrome, switch of replacement therapy from tablet to liquid LT4 should be tested before increasing the dose of LT4.

Open access

Taisuke Uchida, Hideki Yamaguchi, Kazuhiro Nagamine, Tadato Yonekawa, Eriko Nakamura, Nobuhiro Shibata, Fumiaki Kawano, Yujiro Asada and Masamitsu Nakazato

Summary

We report a case of rapid pleural effusion after discontinuation of lenvatinib. A 73-year-old woman was diagnosed with poorly differentiated thyroid cancer with right pleural metastasis. Weekly paclitaxel treatment was performed for 18 weeks, but it was not effective. Oral administration of lenvatinib, a multi-target tyrosine kinase inhibitor, reduced the size of cervical and thoracic tumors and lowered serum thyroglobulin levels. Lenvatinib was discontinued on day 28 because of Grade 2 thrombocytopenia and Grade 3 petechiae. Seven days after discontinuation of lenvatinib, the patient was hospitalized because of dyspnea and right pleural effusion. Pleural effusion rapidly improved with drainage and re-initiation of lenvatinib and did not recur. Anorexia caused by lenvatinib led to undernutrition, which resulted in death 13 months after initiation of lenvatinib. Autopsy revealed extensive necrosis with primary and metastatic lesions, suggesting that the patient responded to lenvatinib. Physicians should be aware of the possibility of flare-up in patients with thyroid cancer treated with lenvatinib.

Learning points:

  • Autopsy findings revealed that lenvatinib was efficacious in treating poorly differentiated thyroid cancer without primary lesion resection.

  • Flare-up phenomenon may occur in thyroid cancer treated with lenvatinib.

  • Attention should be paid to flare-up phenomenon within a few days of discontinuing lenvatinib.

Open access

Ilan Rahmani Tzvi-Ran, Judith Olchowski, Merav Fraenkel, Asher Bashiri and Leonid Barski

Summary

A previously healthy 24-year-old female underwent an emergent caesarean section without a major bleeding described. During the first post-operative days (POD) she complained of fatigue, headache and a failure to lactate with no specific and conclusive findings on head CT. On the following days, fever rose with a suspicion of an obstetric surgery-related infection, again with no evidence to support the diagnosis. On POD5 a new-onset hyponatremia was documented. The urine analysis suggested SIADH, and following a treatment failure, further investigation was performed and demonstrated both central hypothyroidism and adrenal insufficiency. The patient was immediately treated with hydrocortisone followed by levothyroxine with a rapid resolution of symptoms and hyponatremia. Further laboratory investigation demonstrated anterior hypopituitarism. The main differential diagnosis was Sheehan’s syndrome vs lymphocytic hypophysitis. Brain MRI was performed as soon as it was available and findings consistent with Sheehan’s syndrome confirmed the diagnosis. Lifelong hormonal replacement therapy was initiated. Further complaints on polyuria and polydipsia have led to a water deprivation testing and the diagnosis of partial central insipidus and appropriate treatment with DDAVP.

Learning points:

  • Sheehan’s syndrome can occur, though rarely, without an obvious major post-partum hemorrhage.

  • The syndrome may resemble lymphocytic hypophysitis clinically and imaging studies may be crucial in order to differentiate both conditions.

  • Hypopituitarism presentation may be variable and depends on the specific hormone deficit.

  • Euvolemic hyponatremia workup must include thyroid function test and 08:00 AM cortisol levels.

Open access

Mara Ventura, Leonor Gomes, Joana Rosmaninho-Salgado, Luísa Barros, Isabel Paiva, Miguel Melo, Diana Oliveira and Francisco Carrilho

Summary

Intracranial germinomas are rare tumors affecting mostly patients at young age. Therefore, molecular data on its etiopathogenesis are scarce. We present a clinical case of a male patient of 25 years with an intracranial germinoma and a 16p11.2 microdeletion. His initial complaints were related to obesity, loss of facial hair and polydipsia. He also had a history of social-interaction difficulties during childhood. His blood tests were consistent with hypogonadotropic hypogonadism and secondary adrenal insufficiency, and he had been previously diagnosed with hypothyroidism. He also presented with polyuria and polydipsia and the water deprivation test confirmed the diagnosis of diabetes insipidus. His sellar magnetic resonance imaging (MRI) showed two lesions: one located in the pineal gland and other in the suprasellar region, both with characteristics suggestive of germinoma. Chromosomal microarray analysis was performed due to the association of obesity with social disability, and the result identified a 604 kb 16p11.2 microdeletion. The surgical biopsy confirmed the histological diagnosis of a germinoma. Pharmacological treatment with testosterone, hydrocortisone and desmopressin was started, and the patient underwent radiotherapy (40 Gy divided in 25 fractions). Three months after radiotherapy, a significant decrease in suprasellar and pineal lesions without improvement in pituitary hormonal deficiencies was observed. The patient is currently under follow-up. To the best of our knowledge, we describe the first germinoma in a patient with a 16p11.2 deletion syndrome, raising the question about the impact of this genetic alteration on tumorigenesis and highlighting the need of molecular analysis of germ cell tumors as only little is known about their genetic background.

Learning points:

  • Central nervous system germ cell tumors (CNSGTs) are rare intracranial tumors that affect mainly young male patients. They are typically located in the pineal and suprasellar regions and patients frequently present with symptoms of hypopituitarism.

  • The molecular pathology of CNSGTs is unknown, but it has been associated with gain of function of the KIT gene, isochromosome 12p amplification and a low DNA methylation.

  • Germinoma is a radiosensitive tumor whose diagnosis depends on imaging, tumor marker detection, surgical biopsy and cerebrospinal fluid cytology.

  • 16p11.2 microdeletion syndrome is phenotypically characterized by developmental delay, intellectual disability and autism spectrum disorders.

  • Seminoma, cholesteatoma, desmoid tumor, leiomyoma and Wilms tumor have been described in a few patients with 16p11.2 deletion.

  • Bifocal germinoma was identified in this patient with a 16p11.2 microdeletion syndrome, which represents a putative new association not previously reported in the literature.

Open access

C Kamath, J Witczak, M A Adlan and L D Premawardhana

Summary

Thymic enlargement (TE) in Graves’ disease (GD) is often diagnosed incidentally when chest imaging is done for unrelated reasons. This is becoming more common as the frequency of chest imaging increases. There are currently no clear guidelines for managing TE in GD. Subject 1 is a 36-year-old female who presented with weight loss, increased thirst and passage of urine and postural symptoms. Investigations confirmed GD, non-PTH-dependent hypercalcaemia and Addison’s disease (AD). CT scans to exclude underlying malignancy showed TE but normal viscera. A diagnosis of hypercalcaemia due to GD and AD was made. Subject 2, a 52-year-old female, was investigated for recurrent chest infections, haemoptysis and weight loss. CT thorax to exclude chest malignancy, showed TE. Planned thoracotomy was postponed when investigations confirmed GD. Subject 3 is a 47-year-old female who presented with breathlessness, chest pain and shakiness. Investigations confirmed T3 toxicosis due to GD. A CT pulmonary angiogram to exclude pulmonary embolism showed TE. The CT appearances in all three subjects were consistent with benign TE. These subjects were given appropriate endocrine treatment only (without biopsy or thymectomy) as CT appearances showed the following appearances of benign TE – arrowhead shape, straight regular margins, absence of calcification and cyst formation and radiodensity equal to surrounding muscle. Furthermore, interval scans confirmed thymic regression of over 60% in 6 months after endocrine control. In subjects with CT appearances consistent with benign TE, a conservative policy with interval CT scans at 6 months after endocrine control will prevent inappropriate surgical intervention.

Learning points:

  • Chest imaging is common in modern clinical practice and incidental anterior mediastinal abnormalities are therefore diagnosed frequently.

  • Thymic enlargement (TE) associated with Graves’ disease (GD) is occasionally seen in view of the above.

  • There is no validated strategy to manage TE in GD at present.

  • However, CT (or MRI) scan features of the thymus may help characterise benign TE, and such subjects do not require thymic biopsy or surgery at presentation.

  • In them, an expectant ‘wait and see’ policy is recommended with GD treatment only, as the thymus will show significant regression 6 months after endocrine control.

Open access

Ohoud Al Mohareb, Mussa H Al Malki, O Thomas Mueller and Imad Brema

Summary

Resistance to thyroid hormone-beta (RTHbeta) is a rare inherited syndrome characterized by variable reduced tissue responsiveness to the intracellular action of triiodothyronine (T3), the active form of the thyroid hormone. The presentation of RTHbeta is quite variable and mutations in the thyroid hormone receptor beta (THR-B) gene have been detected in up to 90% of patients. The proband was a 34-year-old Jordanian male who presented with intermittent palpitations. His thyroid function tests (TFTs) showed a discordant profile with high free T4 (FT4) at 45.7 pmol/L (normal: 12–22), high free T3 (FT3) at 11.8 pmol/L (normal: 3.1–6.8) and inappropriately normal TSH at 3.19 mIU/L (normal: 0.27–4.2). Work up has confirmed normal alpha subunit of TSH of 0.1 ng/mL (normal <0.5) and pituitary MRI showed no evidence of a pituitary adenoma; however, there was an interesting coincidental finding of partially empty sella. RTHbeta was suspected and genetic testing confirmed a known mutation in the THR-B gene, where a heterozygous A to G base change substitutes valine for methionine at codon 310. Screening the immediate family revealed that the eldest son (5 years old) also has discordant thyroid function profile consistent with RTHbeta and genetic testing confirmed the same M310V mutation that his father harbored. Moreover, the 5-year-old son had hyperactivity, impulsivity and aggressive behavior consistent with attention deficit hyperactivity disorder (ADHD). This case demonstrates an unusual co-existence of RTHbeta and partially empty sella in the same patient which, to our knowledge, has not been reported before.

Learning points:

  • We report the coincidental occurrence of RTHbeta and a partially empty sella in the same patient that has not been previously reported.

  • TFTs should be done in all children who present with symptoms suggestive of ADHD as RTHbeta is a common finding in these children.

  • The management of children with ADHD and RTHbeta could be challenging for both pediatricians and parents and the administration of T3 with close monitoring may be helpful in some cases.

  • Incidental pituitary abnormalities do exist in patients with RTHbeta, although extremely rare, and should be evaluated thoroughly and separately.