We describe two cases of SGLT2i-induced euglycaemic diabetic ketoacidosis, which took longer than we anticipated to treat despite initiation of our DKA protocol. Both patients had an unequivocal diagnosis of type 2 diabetes, had poor glycaemic control with a history of metformin intolerance and presented with relatively vague symptoms post-operatively. Neither patient had stopped their SGLT2i pre-operatively, but ought to have by current treatment guidelines.
SGLT2i-induced EDKA is a more protracted and prolonged metabolic derangement and takes approximately twice as long to treat as hyperglycaemic ketoacidosis.
Surgical patients ought to stop SGLT2i medications routinely pre-operatively and only resume them after they have made a full recovery from the operation.
While the mechanistic basis for EDKA remains unclear, our observation of marked ketonuria in both patients suggests that impaired ketone excretion may not be the predominant metabolic lesion in every case.
Measurement of insulin, C-Peptide, blood and urine ketones as well as glucagon and renal function at the time of initial presentation with EDKA may help to establish why this problem occurs in specific patients.
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.
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.
We describe three patients presenting with diabetic ketoacidosis secondary to ketosis prone type 2, rather than type 1 diabetes. All patients were treated according to a standard DKA protocol, but were subsequently able to come off insulin therapy while maintaining good glycaemic control. Ketosis-prone type 2 diabetes (KPD) presenting with DKA has not been described previously in Irish patients. The absence of islet autoimmunity and evidence of endogenous beta cell function after resolution of DKA are well-established markers of KPD, but are not readily available in the acute setting. Although not emphasised in any current guidelines, we have found that a strong family history of type 2 diabetes and the presence of cutaneous markers of insulin resistance are strongly suggestive of KPD. These could be emphasised in future clinical practice guidelines.
Even in white patients, DKA is not synonymous with type 1 diabetes and autoimmune beta cell failure. KPD needs to be considered in all patients presenting with DKA, even though it will not influence their initial treatment.
Aside from markers of endogenous beta cell function and islet autoimmunity, which in any case are unlikely to be immediately available to clinicians, consideration of family history of type 2 diabetes and cutaneous markers of insulin resistance might help to identify those with KPD and are more readily apparent in the acute setting, though not emphasised in guidelines.
Consideration of KPD should never alter the management of the acute severe metabolic derangement of DKA, and phasing out of insulin therapy requires frequent attendance and meticulous and cautious surveillance by a team of experienced diabetes care providers.
Co-secretion of growth hormone (GH) and prolactin (PRL) from a single pituitary adenoma is common. In fact, up to 25% of patients with acromegaly may have PRL co-secretion. The prevalence of acromegaly among patients with a newly diagnosed prolactinoma is unknown. Given the possibility of mixed GH and PRL co-secretion, the current recommendation is to obtain an insulin-like growth factor-1 (IGF-1) in patients with prolactinoma at the initial diagnosis. Long-term follow-up of IGF-1 is not routinely done. Here, we report two cases of well-controlled prolactinoma on dopamine agonists with the development of acromegaly 10–20 years after the initial diagnoses. In both patients, a mixed PRL/GH-cosecreting adenoma was confirmed on the pathology examination after transsphenoidal surgery (TSS). Therefore, periodic routine measurements of IGF-1 should be considered regardless of the duration and biochemical control of prolactinoma.
Acromegaly can develop in patients with well-controlled prolactinoma on dopamine agonists.
The interval between prolactinoma and acromegaly diagnoses can be several decades.
Periodic screening of patients with prolactinoma for growth hormone excess should be considered and can lead to an early diagnosis of acromegaly before the development of complications.
Hadara RubinfeldInstitute of Endocrinology and Felsenstein Medical Research Center, Rabin Medical Center, Petach Tikva, 49100, Israel Sackler School of Medicine, Tel-Aviv University, Tel Aviv, 69978, Israel
Ilan ShimonInstitute of Endocrinology and Felsenstein Medical Research Center, Rabin Medical Center, Petach Tikva, 49100, Israel Sackler School of Medicine, Tel-Aviv University, Tel Aviv, 69978, Israel
Acromegaly due to ectopic GHRH secretion from a neuroendocrine tumor (NET) is rare and comprises <1% of all acromegaly cases. Herein we present a 57-year-old woman with clinical and biochemical features of acromegaly and a 6 cm pancreatic NET (pNET), secreting GHRH and calcitonin. Following surgical resection of the pancreatic tumor, IGF1, GH and calcitonin normalized, and the clinical features of acromegaly improved. In vitro studies confirmed that the tumor secreted large amounts of both GHRH and calcitonin, and incubation of pNET culture-derived conditioned media stimulated GH release from a cultured human pituitary adenoma. This is a unique case of pNET secreting both GHRH and calcitonin. The ability of the pNET-derived medium to stimulate in vitro GH release from a human pituitary-cell culture, combined with the clinical and hormonal remission following tumor resection, confirmed the ectopic source of acromegaly in this patient.
Signs, symptoms and initial work-up of acromegaly due to ectopic GHRH secretion are similar to pituitary-dependent acromegaly. However, if no identifiable pituitary lesion is found, somatostatin receptor scan and further imaging (CT, MRI) should be performed.
Detection of GHRH in the blood and in the tumor-derived medium supports the diagnosis of ectopic GHRH secretion.
Functional bioactivity of pNET-secreted GHRH can be proved in vitro by releasing GH from human pituitary cells.