Browse

You are looking at 1 - 10 of 12 items for :

  • Face - coarse features x
Clear All
Open access

Nicholas J Theis, Toby Calvert, Peter McIntyre, Stephen P Robertson and Benjamin J Wheeler

Summary

Cantu syndrome, or hypertrichotic osteochondrodysplasia, is a rare, autosomal dominant genetically heterogeneous disorder. It is characterized by hypertrichosis, cardiac and skeletal anomalies and distinctive coarse facial features. We report a case where slowed growth velocity at 13 years led to identification of multiple pituitary hormone deficiencies. This adds to other reports of pituitary abnormalities in this condition and supports inclusion of endocrine monitoring in the clinical surveillance of patients with Cantu syndrome.

Learning points:

  • Cantu syndrome is a rare genetic disorder caused by pathogenic variants in the ABCC9 and KCNJ8 genes, which result in gain of function of the SUR2 or Kir6.1 subunits of widely expressed KATP channels.
  • The main manifestations of the syndrome are varied, but most commonly include hypertrichosis, macrosomia, macrocephaly, coarse ‘acromegaloid’ facies, and a range of cardiac defects.
  • Anterior pituitary dysfunction may be implicated in this disorder, and we propose that routine screening should be included in the clinical and biochemical surveillance of patients with Cantu syndrome.
Open access

Shinichiro Teramoto, Yuichi Tange, Hisato Ishii, Hiromasa Goto, Ikuko Ogino and Hajime Arai

Summary

A 67-year-old woman with a past history of type 2 diabetes mellitus presented with worsening glycemic control. She had some acromegaly symptoms and magnetic resonance imaging demonstrated a pituitary tumor. Endocrinological examination found the resting growth hormone (GH) level within the normal range, but elevated insulin-like growth factor 1 level. A 75 g oral glucose tolerance test showed inadequate suppression of nadir GH levels. Acromegaly due to GH-secreting pituitary tumor was diagnosed. The patient underwent endoscopic transsphenoidal surgery resulting in gross total removal of the tumor and recovered well postoperatively. Histological examination of the tumor showed coexistence of relatively large gangliocytoma cells and pituitary adenoma cells, suggesting mixed gangliocytoma-pituitary adenoma. In addition, colocalization of GH and GH-releasing hormone (GHRH) in pituitary adenoma cells was revealed, so the adenomatous components were more likely to produce GHRH in our mixed gangliocytoma-pituitary adenoma case. Mixed gangliocytoma-pituitary adenoma is very rare, and the present unique case demonstrated only the adenomatous components associated with GHRH production.

Learning points:

  • Sellar gangliocytoma coexisting with pituitary adenoma is recognized as a mixed gangliocytoma-pituitary adenoma and is very rare.
  • A proposed developmental mechanism of growth hormone (GH)-secreting mixed gangliocytoma-pituitary adenoma involves GH-releasing hormone (GHRH) produced by the gangliocytic components promoting the growth of tumor including GH-secreting adenomatous components.
  • Since our present case indicated that the adenomatous components of mixed gangliocytoma-pituitary adenoma could secrete both GH and GHRH simultaneously, progression of GH-secreting mixed gangliocytoma and pituitary adenoma may involve exposure to spontaneously produced GHRH due to the adenomatous components.
Open access

Laura Hamilton Adams and Derick Adams

Summary

Co-secreting TSH and growth hormone pituitary adenomas are rare. We present a case of a 55-year-old woman who presented with symptoms of neck fullness. Ultrasound revealed multiple thyroid nodules and examination revealed several clinical features of acromegaly. She was found to have a co-secreting TSH and growth hormone pituitary macroadenoma. She underwent surgical resection followed by gamma knife radiation, which resulted in complete remission of her TSH and GH-secreting adenoma.

Learning points:

  • TSH-secreting pituitary adenomas are rare and about one-third co-secrete other hormones.
  • Thyroid nodules are common in acromegaly and can be the presenting sign of a growth hormone-secreting pituitary adenoma.
  • In the workup of acromegaly, assessment of other pituitary hormones is essential, even in the absence of symptoms of other pituitary hormone dysfunction.
  • Complete remission of co-secreting GH and TSH pituitary macroadenomas is possible with surgery and radiation alone.
Open access

Athanasios Fountas, Shu Teng Chai, John Ayuk, Neil Gittoes, Swarupsinh Chavda and Niki Karavitaki

Summary

Co-existence of craniopharyngioma and acromegaly has been very rarely reported. A 65-year-old man presented with visual deterioration, fatigue and frontal headaches. Magnetic resonance imaging revealed a suprasellar heterogeneous, mainly cystic, 1.9 × 2 × 1.9 cm mass compressing the optic chiasm and expanding to the third ventricle; the findings were consistent with a craniopharyngioma. Pituitary hormone profile showed hypogonadotropic hypogonadism, mildly elevated prolactin, increased insulin-like growth factor 1 (IGF-1) and normal thyroid function and cortisol reserve. The patient had transsphenoidal surgery and pathology of the specimen was diagnostic of adamantinomatous craniopharyngioma. Post-operatively, he had diabetes insipidus, hypogonadotropic hypogonadism and adrenocorticotropic hormone and thyroid-stimulating hormone deficiency. Despite the hypopituitarism, his IGF-1 levels remained elevated and subsequent oral glucose tolerance test did not show complete growth hormone (GH) suppression. Further review of the pre-operative imaging revealed a 12 × 4 mm pituitary adenoma close to the right carotid artery and no signs of pituitary hyperplasia. At that time, he was also diagnosed with squamous cell carcinoma of the left upper lung lobe finally managed with radical radiotherapy. Treatment with long-acting somatostatin analogue was initiated leading to biochemical control of the acromegaly. Latest imaging has shown no evidence of craniopharyngioma regrowth and stable adenoma. This is a unique case report of co-existence of craniopharyngioma, acromegaly and squamous lung cell carcinoma that highlights diagnostic and management challenges. Potential effects of the GH hypersecretion on the co-existent tumours of this patient are also briefly discussed.

Learning points:

  • Although an extremely rare clinical scenario, craniopharyngioma and acromegaly can co-exist; aetiopathogenic link between these two conditions is unlikely.
  • Meticulous review of unexpected biochemical findings is vital for correct diagnosis of dual pituitary pathology.
  • The potential adverse impact of GH excess due to acromegaly in a patient with craniopharyngioma (and other neoplasm) mandates adequate biochemical control of the GH hypersecretion.
Open access

Syed Ali Imran, Khaled A Aldahmani, Lynette Penney, Sidney E Croul, David B Clarke, David M Collier, Donato Iacovazzo and Márta Korbonits

Summary

Early-onset acromegaly causing gigantism is often associated with aryl-hydrocarbon-interacting receptor protein (AIP) mutation, especially if there is a positive family history. A15y male presented with tiredness and visual problems. He was 201 cm tall with a span of 217 cm. He had typical facial features of acromegaly, elevated IGF-1, secondary hypogonadism and a large macroadenoma. His paternal aunt had a history of acromegaly presenting at the age of 35 years. Following transsphenoidal surgery, his IGF-1 normalized and clinical symptoms improved. He was found to have a novel AIP mutation destroying the stop codon c.991T>C; p.*331R. Unexpectedly, his father and paternal aunt were negative for this mutation while his mother and older sister were unaffected carriers, suggesting that his aunt represents a phenocopy.

Learning points:

  • Typical presentation for a patient with AIP mutation with excess growth and eunuchoid proportions.
  • Unusual, previously not described AIP variant with loss of the stop codon.
  • Phenocopy may occur in families with a disease-causing germline mutation.
Open access

Khaled Aljenaee, Sulaiman Ali, Seong Keat Cheah, Owen MacEneaney, Niall Mulligan, Neil Hickey, Tommy Kyaw Tun, Seamus Sreenan and John H McDermott

Markedly elevated androgen levels can lead to clinical virilization in females. Clinical features of virilization in a female patient, in association with biochemical hyperandrogenism, should prompt a search for an androgen-producing tumor, especially of ovarian or adrenal origin. We herein report the case of a 60-year-old woman of Pakistani origin who presented with the incidental finding of male pattern baldness and hirsutism. Her serum testosterone level was markedly elevated at 21 nmol/L (normal range: 0.4–1.7 nmol/L), while her DHEAS level was normal, indicating a likely ovarian source of her elevated testosterone. Subsequently, a CT abdomen-pelvis was performed, which revealed a bulky right ovary, confirmed on MRI of the pelvis as an enlarged right ovary, measuring 2.9 × 2.2 cm transaxially. A laparoscopic bilateral salpingo-oophorectomy was performed, and histopathological examination and immunohistochemistry confirmed the diagnosis of a Leydig cell tumor, a rare tumor accounting for 0.1% of ovarian tumors. Surgical resection led to normalization of testosterone levels.

Learning points:

  • Hirsutism in postmenopausal women should trigger suspicion of androgen-secreting tumor
  • Extremely elevated testosterone level plus normal DHEAS level point toward ovarian source
  • Leydig cell tumor is extremely rare cause of hyperandrogenicity
Open access

Alfredo Di Cerbo, Federica Pezzuto and Alessandro Di Cerbo

Summary

Graves’ disease, the most common form of hyperthyroidism in iodine-replete countries, is associated with the presence of immunoglobulins G (IgGs) that are responsible for thyroid growth and hyperfunction. In this article, we report the unusual case of a patient with acromegaly and a severe form of Graves’ disease. Here, we address the issue concerning the role of growth hormone (GH) and insulin-like growth factor 1 (IGF1) in influencing thyroid function. Severity of Graves’ disease is exacerbated by coexistent acromegaly and both activity indexes and symptoms and signs of Graves’ disease improve after the surgical remission of acromegaly. We also discuss by which signaling pathways GH and IGF1 may play an integrating role in regulating the function of the immune system in Graves’ disease and synergize the stimulatory activity of Graves’ IgGs.

Learning points:

  • Clinical observations have demonstrated an increased prevalence of euthyroid and hyperthyroid goiters in patients with acromegaly.
  • The coexistence of acromegaly and Graves’ disease is a very unusual event, the prevalence being <1%.
  • Previous in vitro studies have showed that IGF1 synergizes the TSH-induced thyroid cell growth-activating pathways independent of TSH/cAMP/PKA cascade.
  • We report the first case of a severe form of Graves’ disease associated with acromegaly and show that surgical remission of acromegaly leads to a better control of symptoms of Graves’ disease.
Open access

Noor Rafhati Adyani Abdullah, Wong Lok Chin Jason and Azraai Bahari Nasruddin

Summary

Pachydermoperiostosis is a very rare osteoarthrodermopathic disorder whose clinical and radiographic presentations may mimic those of acromegaly. In the evaluation of patients with acromegaloid appearances, pachydermoperiostosis should be considered as a differential diagnosis. In this article, we report a 17-year-old boy who presented with 2-year history of acral enlargement and facial appearance changes associated with joint pain and excessive sweating. He had been investigated extensively for acromegaly, and the final diagnosis was pachydermoperiostosis.

Learning points

  • There is a broad range of differential diagnosis for acromegaloid features such as acromegaly, pseudoacromegaly with severe insulin resistance, Marfan’s syndrome, McCune–Albright and a rare condition called pachydermoperiostosis.
  • Once a patient is suspected to have acromegaly, the first step is biochemical testing to confirm the clinical diagnosis, followed by radiologic testing to determine the cause of the excess growth hormone (GH) secretion. The cause is a somatotroph adenoma of the pituitary in over 95 percent of cases.
  • The first step is measurement of a serum insulin-like growth factor 1 (IGF1). A normal serum IGF1 concentration is strong evidence that the patient does not have acromegaly.
  • If the serum IGF1 concentration is high (or equivocal), serum GH should be measured after oral glucose administration. Inadequate suppression of GH after a glucose load confirms the diagnosis of acromegaly.
  • Once the presence of excess GH secretion is confirmed, the next step is pituitary magnetic resonance imaging (MRI).
  • Atypical presentation warrants revision of the diagnosis. This patient presented with clubbing with no gigantism, which is expected in adolescent acromegalics as the growth spurt and epiphyseal plate closure have not taken place yet.
Open access

Melissa H Lee, Penelope McKelvie, Balasubramanian Krishnamurthy, Yi Yuen Wang and Carmela Caputo

Summary

Most cases of acromegaly are due to growth hormone (GH)-secreting pituitary adenomas arising from somatotroph cells. Mixed pituitary adenoma and gangliocytoma tumours are rare and typically associated with hormonal hypersecretion, most commonly GH excess. Differentiating these mixed tumours from conventional pituitary adenomas can be difficult pre-operatively, and careful histological analysis after surgical resection is key to differentiating the two entities. There is little literature addressing the possible mechanisms for the development of mixed pituitary adenoma–gangliocytomas; however, several hypotheses have been proposed. It still remains unclear if these mixed tumours differ from a clinical perspective to pituitary adenomas; however, the additional neural component of the gangliocytoma does not appear to modify the aggressiveness or risk of recurrence after surgical resection. We report a unique case of acromegaly secondary to a mixed GH-secreting pituitary adenoma, co-existing with an intrasellar gangliocytoma.

Learning points:

  • Acromegaly due to a mixed GH-secreting pituitary adenoma and intrasellar gangliocytoma is rare.
  • These mixed tumours cannot be distinguished easily from ordinary pituitary adenomas on the basis of clinical, endocrine or neuroradiologic findings, and histological analysis is required for a definitive diagnosis.
  • Surgical resection is usually sufficient to provide cure, without the need for adjuvant therapy.
  • These mixed tumours appear to have a good prognosis although the natural history is not well defined.
  • The pathogenesis of these mixed tumours remains debatable, and ongoing research is required.
Open access

Ruth Mangupli, Adrian F Daly, Elvia Cuauro, Paul Camperos, Jaime Krivoy and Albert Beckers

Summary

A 20-year-old man with an 8-year history of progressive enlargement of his hands and feet, coarsening facial features, painful joints and thickened, oily skin was referred for investigation of acromegaly. On examination, the subject was of normal height and weight. He had markedly increased skin thickness around the forehead, eyelids and scalp with redundant skin folds. Bilateral painful knee swelling was accompanied by enlargement of the extremities, and his fingers were markedly clubbed. Routine hematological, biochemical and hormonal blood tests, including GH and IGF-1 were normal. The clinical picture suggested primary hypertrophic osteoarthropathy (PHOA) rather than acromegaly and radiological studies were supportive of this, demonstrating increased subperiosteal bone formation and increased bone density and cortical thickening. There was widespread joint disease, with narrowing of joint spaces, whereas the knees demonstrated effusions and calcification. A skull X-ray revealed calvarial hyperostosis and a normal sellar outline. Family history was negative. Genetic studies were performed on peripheral blood leukocyte DNA for mutations in the two genes associated with PHOA, 15-hydroxyprostaglandin dehydrogenase (HPGD; OMIM: 601688) and solute carrier organic anion transporter family member 2A1 (SLCO2A1; OMIM: 601460). The sequence of HPGD was normal, whereas the subject was homozygous for a novel pathological variant in SLCO2A1, c.830delT, that predicted a frameshift and early protein truncation (p.Phe277Serfs*8). PHOA, also known as pachydermoperiostosis, is a rare entity caused by abnormal prostaglandin E2 metabolism, and both HPGD and SLCO2A1 are necessary for normal prostaglandin E2 handling. High prostaglandin levels lead to bone formation and resorption and connective tissue inflammation causing arthropathy, in addition to soft tissue swelling.

Learning points:

  • The differential diagnosis of enlarged extremities, coarsened facial features, skin changes and increased sweating in suspected acromegaly is quite limited and primary hypertrophic osteoarthropathy (PHOA) is one of the few conditions that can mimic acromegaly at presentation.
  • PHOA is not associated with abnormalities in GH and IGF-1 secretion and can be readily differentiated from acromegaly by hormonal testing.
  • Clubbing in the setting of diffuse enlargement of joints and extremities in addition to skin changes should alert the physician to the possibility of PHOA, as clubbing is not a usual feature of acromegaly. Underlying causes of secondary hypertrophic osteoarthroapthy (e.g. bronchial neoplasia) should be considered.
  • PHOA is a very rare condition caused by abnormalities in prostaglandin metabolism and has two known genetic causes (HPGD and SLCO2A1 mutations).
  • SLCO2A1 gene mutations lead usually to autosomal recessive PHOA; fewer than 50 SLCO2A1 mutations have been described to date and the current case is only the second in a Hispanic patient.
  • Treatment of primary hypertrophic osteoarthropathy is focused on the management of joint pain usually in the form of non-steroidal anti-inflammatory drug therapy.