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*For medical professionals only
Don't rush to diagnose when your blood sugar rises!
Diabetes, a disease
that is all too familiar to endocrinologists.
Anemia is also common for physicians
.
But if there is such a case that links these two diseases together, can you guess what the situation is? Today, let's follow the footsteps of Liu Wei, deputy chief physician of the Department of Metabolic Endocrinology of the Second Xiangya Hospital of Central South University, and take a look at this diabetic patient who needs to be carefully classified and diagnosed~I Case Introduction
22-year-old male, a college student, In 2014 (14 years old), the patient underwent bone marrow transplantation for "thalassemia", pretreatment before busulfan transplantation, dry mouth, polydipsia, polyuria during postoperative dexamethasone and tacrolimus, diagnosed "diabetes" in the hospital, used insulin hypoglycemic therapy, and had poor blood sugar control
.
After stopping glucocorticoids in 2015, blood glucose was measured normally, insulin was stopped on his own, and blood glucose
was not monitored.
In March 2022, he had dry mouth, polydipsia, polyuria, polyphagia and weight loss, and the local hospital found diabetes and diabetic ketosis, and came to the Second Xiangya Hospital of Central South University for treatment in order to seek treatment
.
Anamnesis: Diagnosed with thalassaemia in 2000 (8 months of age) with monthly blood
transfusions for 14 years.
In 2014, he underwent bone marrow transplantation, corrected anemia after surgery, was diagnosed with bilateral osteonecrosis of the femoral head in 2016, and underwent "minimally invasive surgery" (details unknown), and currently has difficulty squatting and long-term walking pain in both hips
.
No history of smoking, alcohol consumption, history of water exposure to schistosomiasis, and denial of toxic exposure
.
Both parents are carriers of the thalassemia gene, and family genetic history
of diabetes, coronary heart disease, hypertension, thyroid disease and so on is denied.
Denial of history of
other autoimmune diseases.
Physical examination: body temperature: 36.
1 ° C, pulse: 90 beats/min, breathing: 20 beats/min, blood pressure:
100/72mmHg
.
Height: 168cm, weight: 45kg, BMI: 15.
9kg/m2, lame, no obvious pigmentation
on the skin.
Clear, cardiopulmonary (-), soft abdomen, no tenderness and abdominal muscle tension, 1 cm under the ribs, tough, neat
edges.
The spleen is 4 cm below the ribs, the bowel sounds are normal, and there is no edema
in both lower extremities.
The voice is high-pitched, beardless, and armpit hairless
.
Further examination of the external genitalia was carried out, and it was found that: vulvar Tanner stage 2, pubic hair is sparse, inverted triangular distribution, bilateral testicular volume 5ml
.
The penis is short, the length of penis traction is 6.
5 cm, the scrotum is unpigmented, and there are no wrinkles
.
Seeing this, did you find something special about this case? Have patients been concerned about abnormalities in their sexual development? With this question, the doctor continued to consult again.
.
.
.
Multiple examinations, the diseases of each system are revealed
This question was asked, and he did check his own situation
.
As early as 2017 (17 years old), he was hospitalized in the hospital for "growth retardation for 6 years", and was diagnosed with "growth retardation hypergonadotropic hypogonadism growth hormone deficiency"
.
The result of the inspection is shown in the following figure:
Figure 1: Results of an out-of-hospital inspection in June 2017
After communicating with the patient, the doctor at that time gave "HCG 2000U/time intramuscular injection twice a week" treatment.
After medication, the patient felt that the testicles enlarged, the penis grew, morning erection and sperm loss, and the height increased from 160cm to 168cm (note that this is without the use of growth hormone).
In 2021, due to difficulties in purchasing drugs, he stopped HCG on his own, and he still had erections and sperm
loss.
Through the above communication and physical examination, the doctor gave the following diagnosis
.
Diabetes classification to be determined: diabetic ketosis sexual developmental retardation due to hepatosplenomegaly, chato thalassemia bone marrow transplantation due to bilateral femoral head necrosis
At the same time, the doctor also further refined the auxiliary examination results
.
Blood count: WBC count 4.
06×10 9/L, hemoglobin 138 g/L, RBC count 4.
44×10 12/L, platelet count 61×109/L ↓
.
Urinalysis: urine ketone 1+ (10mg/dl), urine glucose 3+ (500mg/dl).
Stool routine + OB: normal
.
Liver function: total protein 55.
4 g/L ↓, albumin 35.
1 g/L ↓
.
Lipids: triglycerides 1.
73 mmol/L ↑, HDL cholesterol 0.
72 mmol/L ↓
.
Blood gas analysis, coagulation function, lactic acid, electrolytes, renal function, thyroid function, thyroid self-body, parathyroid hormone (0 minutes, 20 minutes) were normal
.
Islet function
Figure 2: Glucose and C-peptide results on an empty stomach and 120 minutes after meals
β-Hydroxybutyric acid 1.53 mmol/L ↑
.
Glycated hemoglobin 11.
00 % ↑
.
Three pancreatic islet autoantibodies: GAD-Ab, IA-2A, ZnT8-Ab were negative
.
Sensory threshold measurement, extremity vascular Doppler, fundus photography, 24-hour urine protein test: no obvious abnormalities
.
sex hormone
Six sex hormones: luteinizing hormone 10.
37 IU/L ↑, follicle-stimulating maturation hormone 31.
44 IU/L ↑, testosterone 4.
11 nmol/L ↓, pituitary prolactin 13.
26 ug/L, estradiol 0.
10 nmol/L, progesterone 0.
23 ug/L ↓
.
Figure 3: ACTH, cortisol rhythm
Other test results
- ECG: sinus rhythm, enlarged
atrium. - Chest x-ray is not abnormal.
- Bone age X-ray: bone age about 17-18 years old, bilateral avascular necrosis
of the femoral head. - Cardiac ultrasound: no obvious abnormalities
in the intracardiac structure.
Left ventricular systolic function measures the normal range
. - Abdomen + urinary ultrasound: liver, splenomegaly (right liver oblique diameter 137mm, costal about 16mm, spleen thickness about 52mm, length diameter about 126mm, costal about 40mm).
There are no abnormalities
in the urinary tract.
- Scrotal ultrasound: small bilateral testicular measurement (left size 18mm×9mm, right size 20mm×10mm), uneven parenchymal echo, multiple microcalcified sonograms
.
stripping the cocoon,
Is diabetes related to thalassemia?
The medical history is understood, and the test results are out, so how should this case be analyzed?
Deputy Chief Physician Liu Wei divided it into two parts
: endocrine diseases and non-endocrine diseases.
Endocrine diseases
▌The reason for this visit of diabetic patients is diabetes, and they were treated with glucocorticoids + tacrolimus at the age of 14, when the function of pancreatic
islets was unknown and insulin was used
.
After the glucocorticoids were stopped, symptoms "relented"
.
More than a month before this visit, there was "three more and one less" and spontaneous ketosis without special triggers, and the islet function was further impaired
after admission.
Is this glucocorticoid-related diabetes? Type 1 diabetes? Or some other special type of diabetes?
What kind of diabetes is it? The classification of diabetes is the first difficulty in front of doctors
.
▌ Sexual growth retardation
The patient has elevated LH, elevated FSH, and decreased testosterone at the age of 17, but the patient has testicular enlargement and morning erection when using HCG treatment, and has stopped HCG for 1 year
。 The admission examination found testicular volume of 5 ml (2 ml in 2017), vulvar Tanner stage 2, and sex hormone levels suggesting hypergonadotropic hypogonadism
.
So where is it located? What is the cause? What is the relationship with diabetes?
Non-endocrine diseases
▌ Thalassaemia
patients were diagnosed with thalassemia at 8 months of age, and had high frequency blood transfusion therapy for 14 years, and underwent bone marrow transplantation in 2014 (14 years old), and the red line after surgery was normal, but thrombocytopenia and liver and spleen enlarged
。
So does this condition require further treatment?
Let's solve
the above three problems one by one.
About diabetes classification
The patient in this case is an adolescent-onset patient who has used glucocorticoids and tacrolimus, has no family history, and has thalassaemia, repeated blood transfusions, and bone marrow transplantation
.
After stimulation, the C peptide < 600 pmol/L, indicating impaired
islet function.
Islet autoantibodies are negative
.
In the "Chinese Expert Consensus on Diabetes Classification and Diagnosis", it is divided into type 1 diabetes, type 2 diabetes, gestational diabetes, monogenic diabetes, secondary diabetes and undetermined diabetes
.
Based on the above, we can know that the basis for type 1 diabetes is insufficient, the patient is young and thin, and it is not very supportive of the diagnosis of type 2 diabetes, and monogenic diabetes and secondary diabetes are currently not clear
.
About sexual retardation
The patient's vulvar development, sexual differentiation is distinctly male-shaped, and there is no cryptorchidism, so the patient's development in the embryonic stage is not a problem
.
From the perspective of physiological development, the patient's disease development is in early
adolescence.
Of course, this is not enough, let's compare the clinical performance
.
Table 1: The clinical manifestations
of androgen deficiency are not difficult to draw the same conclusion by comparing the table above: the patient is an androgen deficiency
that onset before puberty.
Therefore, what we can know about diseases of the endocrine system are: untyped diabetes and primary hypogonadism of unknown etiology
.
So how to explain it with monism? Just when everyone was puzzled, it occurred to me that there was another disease that had not been discussed, and that was thalassemia
.
The patient has had multiple blood transfusions for 14 years, is it an endocrine system problem secondary to this cause?
Recurrent bleeding can lead to hemochromatosis, which can be classified as primary or secondary, an autochromatic recessive disorder secondary to repeated blood transfusions, red blood cell abnormalities, bone marrow ineffective hematopoiesis, or alcoholic liver disease
.
Diagnostic criteria for secondary hemochromatosis:
(1) have an underlying disease that causes iron overload; (2) increased ferritin; (3) Primary hemochromatosis
was excluded.
Therefore, the patient was immediately perfected for ferritin examination, and it was found that the patient's serum ferritin was very high, reaching 8826.
52 ng/ml ↑, and serum iron was 38.
6 μmol/L ↑
.
In addition, the patient has abnormal red blood cells, and the diagnosis of secondary hemochromatosis is established
.
When repeated blood transfusions or abnormal erythroid hematopoiesis lead to excessive iron metabolic load, the body will produce a large amount of non-ferritin-bound iron, and then non-ferritin-bound iron will selectively deposit its sensitive tissues, so easily affected tissues and organs include endocrine glands, heart, liver, so hemochromatosis or iron overload diseases can explain the history
of diabetes.
However, our common hemochromatosis patients are more likely to have hypogonadotropic hypogonadism (that is, secondary hypogonadism), and such diseases can also attack gonadal tissue, resulting in hypergonadotropic hypogonadism
.
Does hemochromatosis explain the patient's clinical manifestations?
Moreover, Deputy Chief Physician Liu Wei also consulted: some systemic diseases (such as iron overload), and certain drugs (such as glucocorticoids) may affect the function of the testes and hypothalamus or pituitary gland at the same time.
Present with comorbid primary and secondary hypogonadism
.
In most cases, hormone levels are consistent with
the dominant cause.
For example, in men with hemochromatosis, the pituitary gland and testicles are damaged due to iron overload, but this usually presents with a hormonal pattern
of hypogonadism secondary to low testosterone and low gonadotropins.
This is not consistent with the patient's clinical manifestations! She continued to review relevant information and found that for this case, the acquired congenital late-onset testicular disease with elevated FSH, LH and decreased testosterone had the following causes:
(1) Klinefelter syndrome (2) orchitis (3) chemotherapy (4) Testicular radiotherapy (5) Testicular trauma (6) Cryptorchidism (INSL3/LGR8 mutation)
chemoradiotherapy?! The patient has a history of alkylating agent chemotherapy and radiation therapy! This explains why patients have concurrent pituitary, hypothalamic, and testicular impairment
.
In addition to the endocrine system, hemochromatosis also needs to pay attention to the condition of
the liver.
The lifetime incidence of cirrhosis is close to 10%
in untreated patients with hemochromatosis.
In the context of cirrhosis, patients with hemochromatosis are also at risk of developing hepatocellular carcinoma (HCC), which accounts for 45% of deaths
.
Serum ferritin levels above 2000 ng/mL indicate a particular high risk
.
Cardiomyopathy is the second leading cause
of death in this population.
The accumulation of iron in the heart can lead to cardiomyopathy, arrhythmias and heart failure
.
Therefore, the patient was given cardiac MR and liver MR examination
.
Figure 4: Diffuse decreased T2WI signal in liver, pancreas, and spleen; Diffuse hypopituitary T2WI signaling Liver MRI: diffuse hyposignaling of the liver, pancreas, and spleen, due to excessive iron deposition.
Cardiac MRI scan + enhancement: severe iron deposition
in the myocardium.
Contrast MRI scan + enhancement of pituitary MRI: abnormal pituitary signal, considering iron deposition, slightly higher
bilateral basal ganglia T1 signal.
According to all the above conditions of the patient, the diagnosis is finally out:
1.
Thalassaemia Secondary hemochromatosis
secondary diabetes after bone marrow transplantation Diabetes ketosis hypogonadism, hepatomajor, spleen, thrombocytopenia, 2.
Bilateral necrosis of the femoral head 3.
Protein-calorie malnutrition
brief summary
This is a case admitted to the hospital with diabetes and diabetic ketosis, and a detailed physical examination during the diagnosis and treatment found that the patient had sexual retardation and hepatosplenomegaly, combined with the history of long-term blood transfusion of "thalassemia", and finally diagnosed with secondary hemochromatosis related to polyendocrine gland damage
.
In the follow-up symptomatic treatment of endocrine diseases, active iron expulsion therapy for the cause provides positive help
for improving the prognosis of patients.
Li Xia, chief physician of the Department of Metabolic Endocrinology of the Second Xiangya Hospital of Central South University, emphasized in her comments that accurate classification of diabetes is particularly important for patients, and only by identifying the cause can patients be given the most suitable diagnosis and treatment plan
.
In this case, it was through detailed medical history of the patient that the cause was clarified, and a good treatment effect
was finally obtained.
Where can I see more clinical knowledge? Come to the "doctor's station" and take a look 👇
